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1.
Bol. latinoam. Caribe plantas med. aromát ; 23(2): 214-228, mar. 2024. tab, graf
Article in Spanish | LILACS | ID: biblio-1552134

ABSTRACT

Cancer cells modify lipid metabolism to proliferate, Passiflora edulis ( P. edulis ) fruit juice (ZuFru) has antitumor activity, but whether a mechanism is through modulation of cell lipids is unknown. T o establish if ZuFru modifies cholesterol and triglycerides in SW480 and SW620. ZuFru composition was studied by phytochemical march; antiproliferative activity by sulforhodamine B, cholesterol , and triglycerides by Folch method. Z ufru contains anthocyanins, flavonoids, alkaloids , and tannins. Cell lines showed differences in their growth rate ( p =0.049). At 39.6 µg/m L of ZuFru, cell viability was decreased: SW480 (45.6%) and SW620 (45.1%). In SW480, cholesterol (44.6%) and triglycerides (46.5%) decreased; In SW620, cholesterol decreased 14.8% and triglycerides increased 7%, with significant differences for both lines. A ntiproliferative activity of ZuFru could be associated with the inhibition of intracellular biosynthesis of cholesterol and triglycerides in SW480. Action mechanisms need to be further investigated.


Las células cancerosas modifican el metabolismo lipídico para proliferar; el zumo de fruta (ZuFru) de Passiflora edulis ( P. edulis ) tiene activida d antitumoral, sin embargo, se desconoce si se involucran los lípidos celulares. E stablecer si ZuFru modifica colesterol y triglicéridos en células SW480 y SW620. C omposición del ZuFru, actividad antiproliferativa, colesterol y triglicéridos. Se encontraro n antocianinas, flavonoides, alcaloides y taninos. Las líneas celulares mostraron diferencias en su tasa de crecimiento ( p =0 . 049); ZuFru 39,6 µg/ml se disminuyó la viabilidad celular; SW480 (45,6%) y SW620 (45,1%); en SW480 colesterol (44,6%) y triglicérid os (46,5%) en SW620, colesterol (14,8%) y los triglicéridos aumentaron 7%, con diferencias significativas para ambas líneas. La actividad antiproliferativa del ZuFru podría estar asociada a la inhibición de la biosíntesis intracelular de colesterol y de tr iglicéridos en SW480, pero no en SW620. Estos mecanismos de acción deben ser fuertemente investigados.


Subject(s)
Plant Extracts/administration & dosage , Colorectal Neoplasms/drug therapy , Passiflora/chemistry , Fruit and Vegetable Juices/analysis , Phenols/analysis , Polysaccharides/analysis , Triglycerides , Flavonoids/analysis , Plant Extracts/chemistry , Cell Survival/drug effects , Cholesterol , Anticarcinogenic Agents , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Antioxidants
2.
Bol. latinoam. Caribe plantas med. aromát ; 23(2): 199-213, mar. 2024. graf
Article in English | LILACS | ID: biblio-1552114

ABSTRACT

To study the effect of 50% ethanol extract of Bougainvillea xbuttiana on the enzymatic activity, cell via bility and cytokine production provoked by the venom of Bothrops jararaca in macro - phages. Three assays were used to study the effects of B. xbuttiana extract on the damage pro - duced by B. jararaca : Enzymatic activity was detected by measuring the proteoly tic and phos - pholipase A2; macrophages cytotoxicity was determined by the MTT method; levels of cytokine were evaluated using ELISA and a biological assay. After treatment with 300 µg/mL B. xbuttiana extract for 30 min, the proteolytic and phospholipase A2 activities of the venom were reduced to 95 and 61%, respectively. In macrophages cultures treated with B. xbuttiana extract combined with venom, the production of TNF - α, IL - 6 and IFN - γ was reduced, whereas IL - 10 was potenti - ated. Our results support the potential effect of the B. xbuttiana extract as a complementary therapy against the toxicity caused by the venom of B . jararaca snakes


Estudiar el efecto del extracto etanólico al 50% de Bougainvillea xbuttiana sobre la actividad enzimática viabilidad celular y producci ón de citoquinas provocada por el veneno de Bothrops jararaca en macrófagos Se utilizaron tres ensayos para estudiar los efectos del extracto de B. xbuttiana sobre el daño producido por B. jararaca : Se detectó actividad enzimática mediante la medición del proteolítico y fosfolipasa A2; la citotoxicidad de los macrófagos se determinó por el método MTT; Los niveles de citoquinas se evaluaron utilizando ELISA y un ensayo biológico. Después del tratamiento con 300 µg/mL de extracto de B. xbuttiana durante 30 mi n, las actividades proteolíticas y de fosfolipasa A2 del veneno se redujeron a 95 y 61%, respectivamente. En cultivos de macrófagos tratados con extracto de B. xbuttiana combinado con veneno, la producción de TNF - α, IL - 6 e IFN - γ se redujeron, mientras que IL - 10 se potenció. Nuestros resultados apoyan el efecto potencial del extracto de B. xbuttiana como terapia complementaria frente a la toxicidad provocada por el veneno de B. jararaca .


Subject(s)
Animals , Female , Mice , Plant Extracts/pharmacology , Crotalid Venoms/antagonists & inhibitors , Nyctaginaceae/chemistry , Enzyme-Linked Immunosorbent Assay , Cell Survival/drug effects , Cytokines , Crotalid Venoms/enzymology , Ethanol , Phospholipases A2 , Macrophages/drug effects , Mice, Inbred BALB C
3.
Int. j. morphol ; 41(6): 1816-1823, dic. 2023. ilus, tab
Article in English | LILACS | ID: biblio-1528777

ABSTRACT

SUMMARY: To evaluate the anti-cancer effects of yeast extract on resistant cells, autophagy and necroptosis were investigated in 5-fluorouracil (5-FU)-resistant colorectal cancer cells. Further underlying characteristics on drug resistance were evaluated, focused on ERK-RSK-ABCG2 linkage. SNU-C5 and 5-FU resistant SNU-C5 (SNU-C5/5-FUR) colorectal cancer cells were adopted for cell viability assay and Western blotting to examine the anti-cancer effects of yeast extract. Yeast extract induced autophagy in SNU-C5 cells with increased Atg7, Atg12-5 complex, Atg16L1, and LC3 activation (LC3-II/LC3-I), but little effects in SNU-C5/5-FUR cells with increased Atg12-5 complex and Atg16L1. Both colorectal cancer cells did not show necroptosis after yeast extract treatment. Based on increased ABCG2 and RSK expression after yeast extract treatment, drug resistance mechanisms were further evaluated. As compared to wild type, SNU-C5/5-FUR cells showed more ABCG2 expression, less RSK expression, and less phosphorylation of ERK. ABCG2 inhibitor, Ko143, treatment induces following changes: 1) more sensitivity at 500 mM 5-FU, 2) augmented proliferation, and 3) less phosphorylation of ERK. These results suggest that protective autophagy in SNU-C5/5-FUR cells with increased ABCG2 expression might be candidate mechanisms for drug resistance. As the ERK responses were different from each stimulus, the feasible mechanisms among ERK-RSK-ABCG2 should be further investigated in 5-FU-resistant CRC cells.


Para evaluar los efectos anticancerígenos del extracto de levadura en células resistentes, se investigaron la autofagia y la necroptosis en células de cáncer colorrectal resistentes al 5-fluorouracilo (5-FU). Además se evaluaron otras características subyacentes de la resistencia a los medicamentos centrándose en el enlace ERK-RSK-ABCG2. Se usaron células de cáncer colorrectal SNU-C5 (SNU-C5/5-FUR) resistentes a SNU-C5 y 5- FU para el ensayo de viabilidad celular y la transferencia Western para examinar los efectos anticancerígenos del extracto de levadura. El extracto de levadura indujo autofagia en células SNU-C5 con mayor activación de Atg7, complejo Atg12-5, Atg16L1 y LC3 (LC3-II/LC3-I), pero pocos efectos en células SNU-C5/5-FUR con aumento de Atg12-5 complejo y Atg16L1. Ambas células de cáncer colorrectal no mostraron necroptosis después del tratamiento con extracto de levadura. Se evaluaron los mecanismos de resistencia a los medicamentos. en base al aumento de la expresión de ABCG2 y RSK después del tratamiento con extracto de levadura.En comparación con las de tipo salvaje, las células SNU-C5/5-FUR mostraron más expresión de ABCG2, menos expresión de RSK y menos fosforilación de ERK. El tratamiento con inhibidor de ABCG2, Ko143, induce los siguientes cambios: 1) más sensibilidad a 5-FU 500 mM, 2) proliferación aumentada y 3) menos fosforilación de ERK. Estos resultados sugieren que la autofagia protectora en células SNU-C5/5-FUR con mayor expresión de ABCG2 podría ser un mecanismo candidato para la resistencia a los medicamentos. Como las respuestas de ERK fueron diferentes de cada estímulo, los mecanismos factibles entre ERK-RSK- ABCG2 deberían investigarse más a fondo en células CCR resistentes a 5-FU.


Subject(s)
Autophagy , Plant Extracts/pharmacology , Colorectal Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Yeasts , Tumor Cells, Cultured , Cell Survival/drug effects , Blotting, Western , Drug Resistance, Neoplasm , Ribosomal Protein S6 Kinases, 90-kDa , Electrophoresis , Fluorouracil , ATP Binding Cassette Transporter, Subfamily G, Member 2 , Necroptosis
4.
Int. j. morphol ; 41(1): 286-296, feb. 2023. ilus, tab, graf
Article in English | LILACS | ID: biblio-1430539

ABSTRACT

SUMMARY: Cancer is the second leading cause of death in the world and colorectal cancer is the only cancer that has shown a sustained increase in mortality in the last decade. In the search for new chemotherapeutic agents against cancer, extremophilic microorganisms have shown to be a potential source to obtain molecules of natural origin and with selective cytotoxic action towards cancer cells. In this work we analyzed the ability of a collection of Antarctic soil bacteria, isolated on Collins Glacier from the rhizosphere of Deschampsia antarctica Desv plant, to secrete molecules capable of inhibiting cell proliferation of a colorectal cancer tumor line. Our results demonstrated that culture supernatants from the Antarctic bacteria K2I17 and MI12 decreased the viability of LoVo cells, a colorectal adenocarcinoma cell line. Phenotypic and genotypic characterization of the Antarctic bacteria showed that they were taxonomically related and nucleotide identity analysis based on the 16S rRNA gene sequence identified the bacterium K2I17 as a species belonging to the genus Bacillus.


El cáncer es la segunda causa de muerte en el mundo y el cáncer colorrectal es el único que presenta un aumento sostenido de la mortalidad en la última década. En la búsqueda de nuevos agentes quimioterapeúticos contra el cáncer, se ha propuesto a los microorganismos extremófilos como una fuente potencial para obtener moléculas de origen natural y con acción citotóxica selectiva hacia las células cancerígenas. En este trabajo analizamos la capacidad de una colección de bacterias de suelo antártico, aisladas en el glaciar Collins desde rizosfera de la planta de Deschampsia antarctica Desv, de secretar moléculas capaces de inhibir la proliferación celular de una línea tumoral de cáncer colorrectal. Nuestros resultados demostraron que los sobrenadantes de cultivo de las bacterias antárticas K2I17 y MI12 disminuyeron la viabilidad de la línea celular de adenocarcinoma colorrectal LoVo, en un ensayo de reducción metabólica de MTT. La caracterización fenotípica y genotípica de las bacterias antárticas, demostró que estaban relacionadas taxonómicamente y el análisis de la identidad nucleotídica en base a la secuencia del gen ARNr 16S identificó a la bacteria K2I17 como una especie perteneciente al género Bacillus.


Subject(s)
Humans , Soil Microbiology , Bacillus/physiology , Colorectal Neoplasms/drug therapy , Cell Proliferation/drug effects , Phenotype , Bacillus/isolation & purification , Bacillus/genetics , In Vitro Techniques , RNA, Ribosomal, 16S , Adenocarcinoma/drug therapy , Cell Survival/drug effects , Polymerase Chain Reaction , Cell Line, Tumor/drug effects , Genotype , Antarctic Regions
5.
Bol. latinoam. Caribe plantas med. aromát ; 21(5): 646-653, sept. 2022. tab, graf
Article in English | LILACS | ID: biblio-1553790

ABSTRACT

Lippia graveolens HBK (Verbenaceae) is an aromatic herb of economic importance in Mexico, known as oregano. The leaves are used as condiments, and people use this species for respiratory and digestive disorders. The aim of this work was to evaluate the cytotoxic effect of ethanolic extracts obtained from free-oil leaves (L9) and stem (S15), against lung cancer cell line SK-LU-1, through tetrazolium salt (MTT) assay. Extracts concentrations of 0.3 to 300 µg/mL were used and HFF-1 as normal control cells. Both L9 and S15 extracts, showed cytotoxic effect, although stem was stronger than leaves and without damage to normal cell control. The phenolic compounds caffeic acid and acacetin werein higher concentration in L9, whereas naringenin, taxifolin, eriodictyol, luteolin, and apigenin had higher concentrations in S15. The ethanolic extracts of L. graveolens have excellent cytotoxic activity, and have a wide possibility of use in lung cancer treatment.


Lippia graveolens HBK. (Verbenaceae) es una hierba aromática de importancia económica en México, conocida como orégano. Las hojas se usan como condimento y en medicina tradicional se utiliza para aliviar malestares respiratorios y digestivos. El objetivo de este trabajo fue evaluar el efecto citotóxico de extractos etanólicos obtenidos de hojas sin aceite (L9) y tallo (S15), sobre la línea celular de cáncer de pulmón SK-LU-1, mediante el ensayo de la sal de tetrazolium (MTT). Los extractos se aplicaron a concentraciones de 0,3 a 300 µg/mL y se utilizaron células HFF-1 como control normal. Tanto los extractos L9 como S15 mostraron efecto citotóxico, aunque el efecto del tallo fue mayor al de las hojas y sin daño al control celular normal. Los compuestos fenólicos ácido cafeico y acacetina se encontraron en mayor concentración en L9, mientras que naringenina, taxifolina, eriodictyol, luteolina y apigenina tuvieron mayor concentración en S15. Los extractos etanólicos de L. graveolens tienen una excelente actividad citotóxica, con amplia posibilidad de utilizar en el tratamiento de cáncer de pulmón.


Subject(s)
Plant Extracts/administration & dosage , Lippia/chemistry , Cell Line, Tumor/drug effects , Lung Neoplasms/drug therapy , Phenols/analysis , Tetrazolium Salts/chemistry , Plant Extracts/chemistry , Cell Survival/drug effects , Plant Stems , Plant Leaves , Ethanol , Gas Chromatography-Mass Spectrometry
6.
Vitae (Medellín) ; 29(3): 1-7, 2022-08-18. Ilustraciones
Article in English | LILACS, COLNAL | ID: biblio-1393174

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is one of the most diagnosed cancers worldwide. Chemoprevention of HCC can be achieved using natural or synthetic compounds that reverse, suppress, detect, or prevent cancer progression. Objectives: In this study, both the antiproliferative effects and luminescent properties of 2'-hydroxychalcones were evaluated. Methods: Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay, spectroscopy assays, and density functional theory (DFT) calculations were used to determine the luminescent properties of 2 ́-hydroxychalcones. Results: Cytotoxic effects of 2 ́-hydroxychalcones were observed over the HepG2 and EA.hy926 cells. Since the chalcone moiety could be used as a fluorescent probe, these compounds may be helpful in cancer diagnosis and tumor localization. They may enable tumor observation and regression through the fluorescence during treatment; therefore, the compounds are a potential candidate as novel anticancer agents acting on human hepatomas. Conclusions: This report describes the chalcones' use as a specific luminescent biomarker in tumor cells. We also report the cellular uptake of 2'-hydroxychalcones, their cellular distribution, and the mechanisms that may be responsible for their cytotoxic effects


ANTECEDENTES: El carcinoma hepatocelular (CHC) es uno de los cánceres más diagnosticados en todo el mundo. La quimio prevención del CHC se puede lograr utilizando compuestos naturales o sintéticos que reviertan, supriman, detecten o prevengan la progresión del cáncer. OBJETIVOS: En este estudio, se investigó tanto los efectos antiproliferativos como las propiedades luminiscentes de las 2'-hidroxicalconas. MÉTODOS: La viabilidad celular se evaluó usando el ensayo colorimétrico (MTT), los ensayos de espectroscopia y los cálculos DFT se usaron para determinar las propiedades luminiscentes de las 2 ́-hidroxichalconas. RESULTADOS: Se observaron efectos citotóxicos sobre las líneas celulares del tipo HepG2 y EA.hy926. Dado que la estructura de la 2 ́-hidroxichalcona puede ser usada como sonda fluorescente, estos compuestos pueden ser útiles en el diagnóstico del cáncer y la localización del tumor, ya que pueden permitir la observación a través de la fluorescencia y la regresión del tumor durante el tratamiento, por lo que son candidatas potenciales como nuevos agentes anticancerígenos que podrían actuar sobre hepatomas humanos. CONCLUSIONES: Este trabajo describe el uso de las 2 ́-hidroxichalconas como un biomarcador luminiscente específico para células tumorales. También informamos la captación celular de 2>-hidroxicalconas, su distribución celular y los mecanismos que pueden ser responsables de sus efectos citotóxicos


Subject(s)
Humans , Biomarkers, Tumor , Cell Survival/drug effects , Chalcones/pharmacology , Luminescent Agents , Antineoplastic Agents/pharmacology , Hep G2 Cells/drug effects
7.
Int. j. morphol ; 40(1): 91-97, feb. 2022. ilus
Article in English | LILACS | ID: biblio-1385597

ABSTRACT

SUMMARY: Carnosine is known as a natural dipeptide, which inhibits the proliferation of tumor cells throughout its action on mitochondrial respiration and cell glycolysis. However, not much is known about its effects on the metabolism of healthy cells. We explored the effects of Karnozin EXTRA® capsule with different concentrations of L-carnosine, on the cell viability and the expressions of intermediate filament vimentin (VIM) and superoxide dismutase (SOD2) in normal fibroblasts BHK-21/C13. Furthermore, we investigated its action on the energy production of these cells. Cell viability was quantified by the MTT assay. The Clark oxygen electrode (Oxygraph, Hansatech Instruments, England) was used to measure the "intact cell respiration rate", state 3 of ADP-stimulated oxidation, maximum oxidation capacity and the activities of complexes I, II and IV. Results showed that Karnozin EXTRA® capsule in concentrations of 2 and 5 mM of L-carnosine did not induce toxic effects and morphological changes in treated cells. Our data revealed a dose-dependent immunofluorescent signal amplification of VIM and SOD2 in the BHK-21/C13 cell line. This supplement substantially increased the recorded mitochondrial respiration rates in the examined cell line. Due to the stimulation of mitochondrial energy production in normal fibroblasts, our results suggested that Karnozin EXTRA® is a potentially protective dietary supplement in the prevention of diseases with altered mitochondrial function.


RESUMEN: La carnosina se conoce como dipéptido natural, que inhibe la proliferación de células tumorales a través de su acción sobre la respiración mitocondrial y la glucólisis celular. Sin embargo, no se sabe mucho de sus efectos sobre el metabolismo de las células sanas. Exploramos los efectos de la cápsula Karnozin EXTRA® con diferentes concentraciones de L-carnosina, sobre la viabilidad celular y las expresiones de vimentina de filamento intermedio (VIM) y superóxido dismutasa (SOD2) en fibroblastos normales BHK-21 / C13. Además, estudiamos su acción sobre la producción de energía de estas células. La viabilidad celular se cuantificó mediante el ensayo MTT. Se utilizó el electrodo de oxígeno Clark (Oxygraph, Hansatech Instruments, Inglaterra) para medir la "tasa de respiración de células intactas", el estado 3 de oxidación estimulada por ADP, la capacidad máxima de oxidación y las actividades de los complejos I, II y IV. Los resultados mostraron que la cápsula de Karnozin EXTRA® en concentraciones de 2 y 5 mM de L- carnosina no indujo efectos tóxicos ni cambios morfológicos en las células tratadas. Nuestros datos revelaron una amplificación de señal inmunofluorescente dependiente de la dosis de VIM y SOD2 en la línea celular BHK-21 / C13. Este suplemento aumentó sustancialmente las tasas de respiración mitocondrial registradas en la línea celular examinada. Debido a la estimulación de la producción de energía mitocondrial en fibroblastos normales, nuestros resultados sugirieron que Karnozin EXTRA® es un suplemento dietético potencialmente protector en la prevención de enfermedades con función mitocondrial alterada.


Subject(s)
Animals , Carnosine/pharmacology , Fibroblasts/drug effects , Kidney/cytology , Superoxide Dismutase/drug effects , Vimentin/drug effects , Biological Assay , Cell Survival/drug effects , Fluorescent Antibody Technique , Cricetinae , Cell Culture Techniques , Energy Metabolism
8.
Int. j. morphol ; 40(5): 1276-1283, 2022. ilus, graf
Article in Spanish | LILACS | ID: biblio-1405294

ABSTRACT

RESUMEN: Las bacteriocinas son péptidos antimicrobianos de síntesis ribosomal secretadas por bacterias. Dentro de estas destaca nisina que posee potenciales usos en terapias antibióticas, como biopreservante de alimentos y probióticos. También se ha descrito que nisina posee citotoxicidad sobre líneas celulares neoplásicas, pero existe poca información de su efecto sobre células tumorales sanguíneas. Debido al potencial uso que presenta nisina, es relevante determinar la toxicidad que presenta sobre líneas celulares tumorales del tipo sanguíneo. Para esto, se realizaron ensayos de actividad hemolítica sobre eritrocitos humanos y de toxicidad sobre células mononucleares de sangre periférica humanas, determinándose que nisina no posee efecto citotóxico sobre este tipo de células normales humanas sanguíneas. Se realizaron también, ensayos de citotoxicidad con líneas celulares tumorales (K562 y U937), con el fin de determinar dosis, tiempo de exposición y selectividad en el efecto tóxico de nisina sobre las células tumorales humanas. Estos ensayos muestran que nisina presenta actividad citotóxica sobre líneas celulares K562 y U937 a las 72 h de exposición, a una concentración de 40 µg/mL, que corresponde a 100 veces la concentración mínima inhibitoria (MIC) usada para su acción sobre bacterias. Al comparar el efecto de nisina sobre células mononucleares de sangre periférica humanas con las líneas tumorales linfoides y mieloides (K562 y U937 respectivamente), se observa un efecto selectivo de nisina sobre las células tumorales sanguíneas.


SUMMARY: Bacteriocins are antimicrobial peptides of ribosomal synthesis secreted by bacteria. Among these, nisin stands out, which has potential uses in antibiotic therapies, as a food bio preservative and probiotics. Nisin has also been reported to have cytotoxicity on neoplastic cell lines, but there is little information on its effect on blood tumor cells. Due to the potential use that nisin presents, it is relevant to determine the toxicity it presents on tumor cell lines of the blood type. For this, hemolytic activity tests were carried out on human erythrocytes and toxicity on human peripheral blood mononuclear cells, determining that nisin does not have a toxic effect on this type of normal human blood cells. Cytotoxicity tests were also carried out with tumor cell lines (K562 and U937), to determine dose, exposure time and selectivity in the toxic effect of nisin on human tumor cells. These tests show that nisin shows cytotoxic activity on K562 and U937 cell lines at 72 h of exposure, at a concentration of 40 µg / mL, which corresponds to 100 times the minimum inhibitory concentration (MIC) used for its action on bacteria. When comparing the effect of nisin on human peripheral blood mononuclear cells with lymphoid and myeloid tumor lines (K562 and U937 respectively), a selective effect of nisin on blood tumor cells is observed.


Subject(s)
Humans , Cell Line, Tumor/drug effects , Anti-Bacterial Agents/pharmacology , Nisin/pharmacology , Staphylococcus aureus/drug effects , Bacteriocins/pharmacology , In Vitro Techniques , Microbial Sensitivity Tests , Cell Survival/drug effects , K562 Cells/drug effects , U937 Cells/drug effects
9.
Article in English | WPRIM | ID: wpr-878319

ABSTRACT

Objective@#Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM @*Methods@#EVs were isolated from the serum of healthy subjects, quantified @*Results@#PM @*Conclusions@#EVs treatment promotes cell survival and attenuates PM


Subject(s)
Humans , Male , Middle Aged , A549 Cells , Air Pollutants/toxicity , Apoptosis/drug effects , Cell Survival/drug effects , Extracellular Vesicles , Particulate Matter/toxicity , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Serum
10.
Article in English | WPRIM | ID: wpr-878359

ABSTRACT

Objective@#This study aimed to use an air-liquid interface (ALI) exposure system to simulate the inhalation exposure of motorcycle exhaust particulates (MEPs) and then investigate the benchmark dose (BMD) of MEPs by evaluating cell relative viability (CRV) in lung epithelial BEAS-2B cells.@*Methods@#The MEPs dose was characterized by measuring the number concentration (NC), surface area concentration (SAC), and mass concentration (MC). BEAS-2B cells were exposed to MEPs at different concentrations @*Results@#Our results reveal that BMD of NC and SAC were estimated by the best-fitting Hill model, while MC was estimated by Polynomial model. The BMDL for CRV following ALI exposure to MEPs were as follows: 364.2#/cm @*Conclusion@#These results indicate that MEPs exposure


Subject(s)
Humans , Benchmarking/statistics & numerical data , Bronchi/physiology , Cell Line , Cell Survival/drug effects , Epithelial Cells/physiology , Motorcycles , Particulate Matter/adverse effects , Vehicle Emissions/analysis
11.
Acta odontol. latinoam ; 33(2): 82-89, Sept. 2020. graf
Article in English | LILACS | ID: biblio-1130737

ABSTRACT

ABSTRACT The aim of this study was to evaluate the degree of conversion, cytotoxicity, solubility and pH of photopolymerizable calciumbased cements submitted to preheating. The degree of conversion was analyzed by Fourier transform infrared, cytotoxicity by the MTT test and solubility through loss of mass. The data were subjected to statistical tests (ANOVA / Tukey's, p<0.05). The photopolymerizable materials showed a low degree of conversion, regardless of preheating. All materials caused a reduction in cell viability at 24 hours and 7 days, with the Dycal (control) being more cytotoxic. Heat had a positive effect on Biocal at 7 days. Dycal is the most soluble material. Heat had no effect on the solubility or pH of the polymerizable materials. It is concluded that photopolymerizable calcium-based cements have a low degree of conversion and are soluble, which results in mild to moderate cytotoxicity.


RESUMO O objetivo do presente estudo foi avaliar o grau de conversão, citotoxicidade, solubilidade e pH de cimentos à base de cálcio fotopolimerizáveis submetidos a pré-aquecimento. O grau de conversão foi analisado por espectroscopia no infravermelho com transformada de Fourier, a citotoxicidade pelo teste de MTT e a solubilidade através da perda de massa. Os dados foram submetidos a testes estatísticos (ANOVA/Tukey, p<0,05). Os materiais fotopolimerizáveis apresentaram baixo grau de conversão, independente do pré-aquecimento. Todos os materiais causaram redução da viabilidade celular nas análises de 24 horas e 7 dias, sendo que o Dycal (controle) apresentouse mais citotóxico e o calor apresentou efeito positivo sobre o Biocal na análise de 7 dias. O Dycal é o material mais solúvel e o calor não causou efeito na solubilidade e pH dos materiais polimerizáveis. Assim, conclui-se que os cimentos à base de cálcio fotopolimerizáveis apresentam baixo grau de conversão e são solúveis, que resulta em citotoxicidade suave e moderada.


Subject(s)
Humans , Calcium Hydroxide/toxicity , Cell Survival/drug effects , Dental Cements/chemistry , Pulp Capping and Pulpectomy Agents/toxicity , Calcium Hydroxide/chemistry , Calcium , Dental Cements/toxicity , Dental Pulp Capping , Light-Curing of Dental Adhesives , Photochemical Processes , Pulp Capping and Pulpectomy Agents/chemistry , Polymerization , Hydrogen-Ion Concentration
12.
Article in Chinese | WPRIM | ID: wpr-879932

ABSTRACT

OBJECTIVE@#To investigate the regulatory effect of iridoid glycoside of radix scrophulariae (IGRS) on endoplasmic reticulum stress induced by oxygen-glucose deprivation and reperfusion @*METHODS@#Rat pheochromocytoma PC12 cells were pretreated with IGRS (50, 100, 200 μg/mL) for 24h, and the @*RESULTS@#The damage caused by OGD/R to PC12 cells was significantly reduced by IGRS, with significant effect on increasing survival rate and reducing LDH release (all @*CONCLUSIONS@#IGRS has neuroprotective effect, which may alleviate cerebral ischemia-reperfusion injury by regulating SERCA2, maintaining calcium balance, and inhibiting endoplasmic reticulum stress-mediated apoptosis.


Subject(s)
Animals , Rats , Cell Survival/drug effects , Down-Regulation/drug effects , Endoplasmic Reticulum Stress/drug effects , Glucose , In Vitro Techniques , Iridoid Glycosides/pharmacology , Oxygen , PC12 Cells , Reperfusion , Reperfusion Injury/prevention & control , Snails/chemistry
13.
Braz. oral res. (Online) ; 34: e013, 2020. graf
Article in English | LILACS | ID: biblio-1089379

ABSTRACT

Abstract This study evaluated the effect of a cyclopentenone-type PG, 15-Deoxy-Δ12,14-PG J2 (15d-PGJ2), and lectin (ScLL) on the viability of human gingival fibroblasts (HGFs), and on IL-6 and TGFβ-1 release by these fibroblasts, stimulated with lipopolysaccharide (LPS). HGFs were stimulated with LPS 10 μg/ml and treated with 15d-PGJ2 1 and 2 μg/ml, and ScLL 2 and 5 μg/ml, for 1 and 3h, and then evaluated for viability by MTT assay. Supernatant was collected to detect IL-6 and TGFβ-1 release, by ELISA. Positive control was cells kept in Dulbecco's Modified Eagle's Medium, and negative control was those kept in LPS. Data were analyzed by ANOVA and Dunnett's test (α = 0.05). No significant difference was found in viability among experimental groups at 1h (p > 0.05). Percentage of ScLL 5 µg/ml viable cells was similar to that of positive control at evaluated periods (p > 0.05), whereas the other groups had lower levels than the positive control (p < 0.05). IL-6 release was statistically higher for ScLL 5 μg/ml and 15d-PGJ2 2 µg/ml at 1h, compared with the other treated groups and positive control (p < 0.05). No significant differences were found among the groups at 3h (p > 0.05), except for ScLL 2 µg/ml and 15d-PGJ2 1 µg/ml, which showed lower IL-6 release compared with that of negative control (p < 0.05). No significant difference was found among the groups for TGFβ-1 release (p > 0.05). Results indicated that ScLL 5 μg/ml did not interfere in viability, and ScLL 2 µg/ml and 15d-PGJ2 1 µg/ml demonstrated reduced IL-6 release. Tested substances had no effect on TGFβ-1 release.


Subject(s)
Humans , Prostaglandin D2/analogs & derivatives , Lipopolysaccharides/pharmacology , Interleukin-6/metabolism , Plant Lectins/pharmacology , Transforming Growth Factor beta1/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Reference Values , Time Factors , Enzyme-Linked Immunosorbent Assay , Prostaglandin D2/pharmacology , Cell Survival/drug effects , Cells, Cultured , Analysis of Variance , Statistics, Nonparametric , Transforming Growth Factor beta1/drug effects , Gingiva/cytology
14.
Braz. arch. biol. technol ; 63: e20190364, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132221

ABSTRACT

Abstract Chronic inflammation is a common indication of several diseases, e.g. asthma, chronic obstructive pulmonary disease (COPD), atherosclerosis, etc. Benzimidazole derivatives are preferable compounds to design new analgesic and anti-inflammatory substances due to their unique biological features. We aimed to investigate the effect of a newly synthesized benzimidazole derivative, ORT-83, on A549 human lung adenocarcinoma cell line. ORT-83 was synthesized, and a non-cytotoxic concentration of ORT-83 on A549 cells was detected with MTT assay. To analyze the anti-inflammatory effect of ORT-83, an inflammatory cell culture model was established by stimulating A549 cell line with IL1-β (10 ng/ml). After 2 hours of treatment with IL1-β to induce inflammation, A549 cells were exposed to ORT-83 (0.78 µg/ml) for 24 hours. Thereafter gene expression analyses were performed with qRT-PCR. We found that ORT-83 significantly suppressed the gene expression levels of the proinflammatory cytokines; IL-6, NFkB, and TNF-α. However, the increased levels of IL-10 (2.8 folds) by IL-1β induction did not change after ORT-83 and/or dexamethasone (Dex: positive control) treatments. While Dex; a COX-2 inhibitor, reduced the COX-2 expression level in inflammatory cells from 10.03 folds to 0.71 folds, ORT-83 reduced its level to 4.37 folds. iNOS expression levels did not change in any experimental groups. In conclusion, we showed that ORT-83 exerted its anti-inflammatory effects by repressing the gene expression of proinflammatory cytokines in the inflammation-induced A549 cell line. Although ORT-83 had a weaker COX-2 inhibitory effect compared to Dex, it was shown to be still a strong anti-inflammatory compound.


Subject(s)
Humans , Benzimidazoles/pharmacology , Drugs, Investigational , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Cell Survival/drug effects , Toxicity Tests , Reverse Transcriptase Polymerase Chain Reaction , A549 Cells
15.
J. appl. oral sci ; 28: e20190215, 2020. graf
Article in English | LILACS, BBO | ID: biblio-1056582

ABSTRACT

Abstract Objective: This study evaluated the angiogenesis-enhancing potential of a tricalcium silicate-based mineral trioxide aggregate (ProRoot MTA), Biodentine, and a novel bioceramic root canal sealer (Well-Root ST) in human dental pulp stem cells (hDPSCs), human periodontal ligament stem cells (hPLSCs), and human tooth germ stem cells (hTGSCs). Methodology: Dulbecco's modified Eagle's medium was conditioned for 24 h by exposure to ProRoot MTA, Biodentine, or Well-Root ST specimens (prepared according to the manufacturers' instructions). The cells were cultured in these conditioned media and their viability was assessed with 3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H tetrazolium (MTS) on days 1, 3, 7, 10, and 14. Angiogenic growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF-2), and vascular endothelial growth factor (VEGF)] were assayed by sandwich enzyme-linked immunosorbent assay (ELISA) on days 1, 7, and 14. Human umbilical vein endothelial cell (HUVEC) migration assays were used to evaluate the vascular effects of the tested materials at 6-8 h. Statistical analyses included Kruskal-Wallis, Mann-Whitney U, and Friedman and Wilcoxon signed rank tests. Results: None of tricalcium silicate-based materials were cytotoxic and all induced a similar release of angiogenic growth factors (PDGF, FGF-2, and VEGF) (p>0.05). The best cell viability was observed for hDPSCs (p<0.05) with all tricalcium silicate-based materials at day 14. Tube formation by HUVECs showed a significant increase with all tested materials (p<0.05). Conclusion: The tricalcium silicate-based materials showed potential for angiogenic stimulation of all stem cell types and significantly enhanced tube formation by HUVECs.


Subject(s)
Humans , Root Canal Filling Materials/pharmacology , Stem Cells/drug effects , Ceramics/pharmacology , Silicates/pharmacology , Calcium Compounds/pharmacology , Angiogenesis Inducing Agents/pharmacology , Periodontal Ligament/cytology , Periodontal Ligament/drug effects , Tooth Germ/cytology , Tooth Germ/drug effects , Biocompatible Materials/pharmacology , Materials Testing , Platelet-Derived Growth Factor/analysis , Platelet-Derived Growth Factor/drug effects , Enzyme-Linked Immunosorbent Assay , Cell Survival/drug effects , Reproducibility of Results , Fibroblast Growth Factor 2/analysis , Fibroblast Growth Factor 2/drug effects , Statistics, Nonparametric , Neovascularization, Physiologic/drug effects , Dental Pulp/cytology , Dental Pulp/drug effects , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor A/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Flow Cytometry
16.
J. appl. oral sci ; 28: e20190105, 2020. tab, graf
Article in English | LILACS | ID: biblio-1056578

ABSTRACT

Abstract Calcium aluminate cement (CAC) has been highlighted as a promising alternative for endodontic use aiming at periapical tissue repair. However, its effects on dental pulp cells have been poorly explored. Objective: This study assessed the impact of calcium chloride (CaCl2) and bismuth oxide (Bi2O3) or zinc oxide (ZnO) additives on odontoblast cell response to CAC. Methodology: MDPC-23 cells were exposed for up to 14 d: 1) CAC with 2.8% CaCl2 and 25% ZnO (CACz); 2) CAC with 2.8% CaCl2 and 25% Bi2O3 (CACb); 3) CAC with 10% CaCl2 and 25% Bi2O3 (CACb+); or 4) mineral trioxide aggregate (MTA), placed on inserts. Non-exposed cultures served as control. Cell morphology, cell viability, gene expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), and dentin matrix protein 1 (DMP-1), ALP activity, and extracellular matrix mineralization were evaluated. Data were compared using ANOVA (α=5%). Results: Lower cell density was detected only for MTA and CACb+ compared with Control, with areas showing reduced cell spreading. Cell viability was similar among groups at days one and three (p>0.05). CACb+ and MTA showed the lowest cell viability values at day seven (p>0.05). CACb and CACb+ promoted higher ALP and BSP expression compared with CACz (p<0.05); despite that, all cements supported ALP activity. Matrix mineralization were enhanced in CACb+ and MTA. Conclusion: In conclusion, CAC with Bi2O3, but not with ZnO, supported the expression of odontoblastic phenotype, but only the composition with 10% CaCl2 promoted mineralized matrix formation, rendering it suitable for dentin-pulp complex repair.


Subject(s)
Humans , Mice , Calcium Compounds/pharmacology , Calcium Compounds/chemistry , Aluminum Compounds/pharmacology , Aluminum Compounds/chemistry , Dental Cements/pharmacology , Dental Cements/chemistry , Dental Pulp/cytology , Dental Pulp/drug effects , Oxides/pharmacology , Oxides/chemistry , Time Factors , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , Bismuth/pharmacology , Bismuth/chemistry , Materials Testing , Calcium Chloride/pharmacology , Calcium Chloride/chemistry , Gene Expression/drug effects , Cell Survival/drug effects , Cells, Cultured , Reproducibility of Results , Silicates/pharmacology , Silicates/chemistry , Drug Combinations , Alkaline Phosphatase/analysis , Alkaline Phosphatase/drug effects , Odontoblasts/drug effects
17.
Braz. j. med. biol. res ; 53(5): e8457, 2020. tab, graf
Article in English | LILACS | ID: biblio-1098118

ABSTRACT

The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/β-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.


Subject(s)
Humans , Skin Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Metal Nanoparticles/administration & dosage , Levulinic Acids/pharmacology , Photochemotherapy , RNA, Neoplasm , Cell Survival/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects
18.
Braz. j. med. biol. res ; 53(5): e9331, 2020. graf
Article in English | LILACS | ID: biblio-1098113

ABSTRACT

The melamine and cyanuric acid (CA) complex has been suggested to cause the toxic effects observed in melamine-contaminated food or milk. However, the cytotoxic and genotoxic effects of co-exposure to melamine and CA are not fully clear. Therefore, the cytotoxic effects of melamine and CA were first examined by co‐exposure in human kidney 293 cells using the MTT assay. During a 24-h period for the three concentrations tested (0.5, 1, and 5 mg/mL), neither melamine nor CA alone showed significant toxic effects on 293 cells at 0.5 mg/mL, while higher concentrations led to decreased in cell viability. However, co-exposure to several combinations of melamine and CA [100:1, 10:1, 1:10, and 1:100 (v:v), at a final concentration of 0.5 mg/mL] did cause cytotoxicity with higher levels of CA leading to higher cytotoxicity. By contrast, while neither melamine nor CA alone induced phosphorylated-H2AX (γH2AX) foci formation, melamine and CA at a 100:1 ratio induced γH2AX foci 24 h post-treatment. The alkaline comet assay also revealed the presence of DNA damage following melamine and CA co-exposure. In vivo assay also revealed the presence of melamine-CA complex in the kidney. These data indicated that the cytotoxic and genotoxic effects of melamine and CA co-exposure differ from those of melamine or CA alone.


Subject(s)
Humans , Animals , Rats , Triazines/toxicity , DNA Damage/drug effects , Cell Survival/drug effects , Kidney/drug effects , Time Factors , Kidney/embryology , Mutagenicity Tests
19.
Einstein (São Paulo, Online) ; 18: eAO4560, 2020. graf
Article in English | LILACS | ID: biblio-1101099

ABSTRACT

ABSTRACT Objective To investigate if ICI 182,780 (fulvestrant), a selective estrogen receptor alpha/beta (ERα/ERβ) antagonist, and G-1, a selective G-protein-coupled receptor (GPER) agonist, can potentially induce autophagy in breast cancer cell lines MCF-7 and SKBr3, and how G-1 affects cell viability. Methods Cell viability in MCF-7 and SKBr3 cells was assessed by the MTT assay. To investigate the autophagy flux, MCF-7 cells were transfected with GFP-LC3, a marker of autophagosomes, and analyzed by real-time fluorescence microscopy. MCF-7 and SKBr3 cells were incubated with acridine orange for staining of acidic vesicular organelles and analyzed by flow cytometry as an indicator of autophagy. Results Regarding cell viability in MCF-7 cells, ICI 182,780 and rapamycin, after 48 hours, led to decreased cell proliferation whereas G-1 did not change viability over the same period. The data showed that neither ICI 182,780 nor G-1 led to increased GFP-LC3 puncta in MCF-7 cells over the 4-hour observation period. The cytometry assay showed that ICI 182,780 led to a higher number of acidic vesicular organelles in MCF-7 cells. G-1, in turn, did not have this effect in any of the cell lines. In contrast, ICI 182,780 and G-1 did not decrease cell viability of SKBr3 cells or induce formation of acidic vesicular organelles, which corresponds to the final step of the autophagy process in this cell line. Conclusion The effect of ICI 182,780 on increasing acidic vesicular organelles in estrogen receptor-positive breast cancer cells appears to be associated with its inhibitory effect on estrogen receptors, and GPER does notseem to be involved. Understanding these mechanisms may guide further investigations of these receptors' involvement in cellular processes of breast cancer resistance.


RESUMO Objetivo Avaliar o efeito dos compostos ICI 182,780 (fulvestranto), um antagonista seletivo dos receptores de estrógeno alfa/beta (REα/REβ), e do G-1, um agonista seletivo de receptores de estrógeno acoplados a proteínas-G (GPER), na possível indução de autofagia em linhagens de câncer de mama MCF-7 e SKBr3, bem como o efeito de G-1 na viabilidade celular. Métodos A viabilidade celular de células MCF-7 e SKBr3 foi avaliada pelo ensaio com MTT. Para investigar a indução da autofagia, células MCF-7 foram transfectadas com GFP-LC3, um marcador de autofagossomos, e analisadas por microscopia de fluorescência em tempo real. As células MCF-7 e SKBr3 foram incubadas com o indicador de compartimentos ácidos laranja de acridina e analisadas por citometria de fluxo como indicativo para autofagia. Resultados Em células MCF-7, o ICI 182,780 e rapamicina após 48 horas levaram à diminuição da viabilidade celular, enquanto o G-1 não alterou a viabilidade no mesmo período de tratamento. Nem o ICI 182,780 e nem o G-1 induziram aumento na pontuação de GFP-LC3 em células MCF-7 até 4 horas. Já os ensaios de citometria de fluxo demonstraram que ICI 182,780 levou ao aumento de compartimentos ácidos em células MCF-7. O G-1 não aumentou estes parâmetros em ambas as linhagens. Por outro lado, ICI 182,780 e G-1 não induziram à redução da viabilidade em células SKBr3 e nem à formação de compartimentos ácidos, como etapa final do processo autofágico. Conclusão O aumento de compartimentos ácidos pelo ICI 182,780 em células de câncer de mama positivas para receptores de estrógeno parece estar associado com seu efeito inibidor de receptores de estrógeno, mas sem o envolvimento de GPER. A compreensão desses mecanismos pode direcionar estudos sobre o envolvimento dos receptores nos processos celulares de resistência do câncer de mama.


Subject(s)
Humans , Female , Autophagy/drug effects , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Receptors, G-Protein-Coupled/agonists , Estrogen Receptor Antagonists/pharmacology , Fulvestrant/pharmacology , Time Factors , Transfection/methods , Cell Survival/drug effects , Blotting, Western , Reproducibility of Results , Analysis of Variance , Sirolimus/pharmacology , Receptors, G-Protein-Coupled/analysis , Estrogen Receptor alpha/antagonists & inhibitors , Estrogen Receptor beta/antagonists & inhibitors , Cell Proliferation/drug effects , MCF-7 Cells , Flow Cytometry/methods
20.
Int. j. morphol ; 37(2): 584-591, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1002262

ABSTRACT

Following the success of the highly active antiretroviral therapy, the potential of multidrug combination regimen for the management of cancer is intensely researched. The anticancer effects of curcumin on some human cell lines have been documented. Lopinavir is a FDA approved protease inhibitor with known apoptotic activities. Dysregulated apoptosis is important for the initiation of cancer while angiogenesis is required for cancer growth and development, this study therefore investigated the effects of the combination of lopinavir and curcumin on cell viability, apoptosis and the mRNA expression levels of key apoptotic and angiogenic genes; BAX, BCL2 and VEGF165b in two human cervical cell lines; human squamous cell carcinoma cells - uterine cervix (HCS-2) and transformed normal human cervical cells (NCE16IIA). The two human cervical cell lines were treated with physiologically relevant concentrations of the agents for 120 h following which BAX, BCL2 and VEGF165b mRNA expression were determined by Real Time qPCR. The Acridine Orange staining for the morphological evaluation of apoptotic cells was also performed. The combination of lopinavir and curcumin up-regulated pro-apoptotic BAX and antiangiogenic VEGF165b but down-regulated the mRNA levels of anti-apoptotic BCL2 mRNA in the human squamous cell carcinoma (HCS-2) cells only. The fold changes were statistically significant. Micrographs from Acridine Orange staining showed characteristic evidence of apoptosis in the human squamous cell carcinoma (HCS-2) cells only. The findings reported here suggest that the combination of curcumin and the FDA approved drug-lopinavir modulate the apoptotic and angiogenic pathway towards the inhibition of cervical cancer.


Tras el éxito de la terapia antirretroviral altamente activa, se investiga intensamente el potencial del régimen de combinación de múltiples fármacos para el tratamiento del cáncer. Se han documentado los efectos anticancerígenos de la curcumina en algunas líneas celulares humanas. Lopinavir es un inhibidor de proteasa aprobado por la FDA con actividades apoptóticas conocidas. La apoptosis disrregulada es importante para el inicio del cáncer, mientras que la angiogénesis es necesaria para el crecimiento y desarrollo del cáncer. Por lo tanto, este estudio investigó los efectos de la combinación de lopinavir y curcumina sobre la viabilidad celular, la apoptosis y los niveles de expresión del ARNm de genes apoptóticos y angiogénicos clave: BAX, BCL2 y VEGF165b en dos líneas celulares cervicales humanas; células de carcinoma de células escamosas humanas: cérvix uterino (HCS-2) y células cervicales humanas transformadas (NCE16IIA). Las dos líneas celulares cervicales humanas se trataron con concentraciones fisiológicamente relevantes de los agentes durante 120 horas, después de lo cual la expresión de ARNm de BAX, BCL2 y VEGF165b se determinó mediante qPCR en tiempo real. También se realizó la tinción con naranja de acridina para la evaluación morfológica de células apoptóticas. La combinación de lopinavir y curcumina reguló incrementando BAX proapoptósicos y VEGF165b antiangiogénicos, pero reguló a la baja los niveles de ARNm del BCL2 antiapoptótico en células de carcinoma de células escamosas humanas (HCS-2) únicamente. Los cambios en el pliegue fueron estadísticamente significativos. Las micrografías de la tinción con naranja de acridina mostraron evidencia característica de apoptosis solo en las células del carcinoma de células escamosas humanas (HCS-2). Los hallazgos reportados aquí sugieren que la combinación de curcumina y el fármaco aprobado por la FDA lopinavir modulan la vía apoptótica y angiogénica hacia la inhibición del cáncer cervical.


Subject(s)
Humans , Female , Carcinoma, Squamous Cell/drug therapy , Uterine Cervical Neoplasms/drug therapy , Curcumin/pharmacology , Lopinavir/pharmacology , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Apoptosis/drug effects , Cell Line, Tumor/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/genetics , bcl-2-Associated X Protein/drug effects , bcl-2-Associated X Protein/genetics , Real-Time Polymerase Chain Reaction
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