Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 10.675
Filtrar
1.
Sci Rep ; 14(1): 12091, 2024 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802425

RESUMO

Estrogen receptor-negative [ER(-)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years, dietary prevention of BC with epigenetically active phytochemicals has received increased attention due to its feasibility, effectiveness, and ease of implementation. In this regard, combinatorial phytochemical intervention enables more efficacious BC inhibition by simultaneously targeting multiple tumorigenic pathways. We, therefore, focused on investigation of the effect of sulforaphane (SFN)-rich broccoli sprouts (BSp) and withaferin A (WA)-rich Ashwagandha (Ash) combination on BC prevention in estrogen receptor-negative [ER(-)] mammary cancer using transgenic mice. Our results indicated that combinatorial BSp + Ash treatment significantly reduced tumor incidence and tumor growth (~ 75%) as well as delayed (~ 21%) tumor latency when compared to the control treatment and combinatorial BSp + Ash treatment was statistically more effective in suppressing BC compared to single BSp or Ash intervention. At the molecular level, the BSp and Ash combination upregulated tumor suppressors (p53, p57) along with apoptosis associated proteins (BAX, PUMA) and BAX:BCL-2 ratio. Furthermore, our result indicated an expressional decline of epigenetic machinery HDAC1 and DNMT3A in mammary tumor tissue because of combinatorial treatment. Interestingly, we have reported multiple synergistic interactions between BSp and Ash that have impacted both tumor phenotype and molecular expression due to combinatorial BSp and Ash treatment. Our RNA-seq analysis results also demonstrated a transcriptome-wide expressional reshuffling of genes associated with multiple cell-signaling pathways, transcription factor activity and epigenetic regulations due to combined BSp and Ash administration. In addition, we discovered an alteration of gut microbial composition change because of combinatorial treatment. Overall, combinatorial BSp and Ash supplementation can prevent ER(-) BC through enhanced tumor suppression, apoptosis induction and transcriptome-wide reshuffling of gene expression possibly influencing multiple cell signaling pathways, epigenetic regulation and reshaping gut microbiota.


Assuntos
Neoplasias da Mama , Epigênese Genética , Microbioma Gastrointestinal , Isotiocianatos , Sulfóxidos , Vitanolídeos , Isotiocianatos/farmacologia , Animais , Vitanolídeos/farmacologia , Sulfóxidos/farmacologia , Feminino , Camundongos , Epigênese Genética/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos Transgênicos , Extratos Vegetais/farmacologia , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Humanos , Brassica/química , Histona Desacetilase 1/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Anticarcinógenos/farmacologia
2.
Vitae (Medellín) ; 31(1): 1-7, 2024-05-03. Ilustraciones
Artigo em Inglês | LILACS, COLNAL | ID: biblio-1538070

RESUMO

Background: Moringa peregrina is widely used in the traditional medicine of the Arabian Peninsula to treat various ailments, because it has many pharmacologically active components with several therapeutic effects. Objective: This study aimed to investigate the inhibitory effect of Moringaperegrina seed ethanolic extract (MPSE) against key enzymes involved in human pathologies, such as angiogenesis (thymidine phosphorylase), diabetes (α-glucosidase), and idiopathic intracranial hypertension (carbonic anhydrase). In addition, the anticancer properties were tested against the SH-SY5Y (human neuroblastoma). Results: MPSE extract significantly inhibited α-glucosidase, thymidine phosphorylase, and carbonic anhydrase with half-maximal inhibitory concentrations (IC50) values of 303.1 ± 1.3, 471.30 ± 0.3, and 271.30 ± 5.1 µg/mL, respectively. Furthermore, the antiproliferative effect of the MPSE was observed on the SH-SY5Y cancer cell line with IC50 values of 55.1 µg/mL. Conclusions: MPSE has interesting inhibitory capacities against key enzymes and human neuroblastoma cancer cell line.


Antecedentes: La Moringa peregrina se utiliza ampliamente en la medicina tradicional de la Península Arábiga para tratar diversas dolencias, ya que posee numerosos componentes farmacológicamente activos con varios efectos terapéuticos. Objetivo: Este estudio tenía como objetivo investigar el efecto inhibidor del extracto etanólico de semillas de Moringaperegrina (MPSE) frente a enzimas clave implicadas en patologías humanas, como la angiogénesis (timidina fosforilasa), la diabetes (α-glucosidasa) y la hipertensión intracraneal idiopática (anhidrasa carbónica). Además, se comprobaron las propiedades anticancerígenas frente al SH-SY5Y (neuroblastoma humano). Resultados: El extracto de MPSE inhibió significativamente la α-glucosidasa, la timidina fosforilasa y la anhidrasa carbónica con concentraciones inhibitorias semimáximas (IC50) de 303,1 ± 1,3, 471,30 ± 0,3 y 271,30 ± 5,1 µg/mL, respectivamente. Además, se observó el efecto antiproliferativo del MPSE en la línea celular del cáncer SH-SY5Y con valores de IC50 de 55,1 µg/mL. Conclusiones: MPSE posee interesantes capacidades inhibitorias frente a enzimas clave y línea celular de neuroblastoma canceroso humano.


Assuntos
Humanos , Anticarcinógenos , Moringa , Inibidores Enzimáticos , alfa-Glucosidases
3.
Nutrients ; 16(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38674816

RESUMO

Colorectal cancer (CRC) accounts for 30% of all cancer cases worldwide and is the second leading cause of cancer-related deaths. CRC develops over a long period of time, and in the early stages, pathological changes can be mitigated through nutritional interventions using bioactive plant compounds. Our study aims to determine the effect of highly purified oat beta-glucan on an animal CRC model. The study was performed on forty-five male Sprague-Dawley rats with azoxymethane-induced early-stage CRC, which consumed feed containing 1% or 3% low molar mass oat beta-glucan (OBG) for 8 weeks. In the large intestine, morphological changes, CRC signaling pathway genes (RT-PCR), and proteins (Western blot, immunohistochemistry) expression were analyzed. Whole blood hematology and blood redox status were also performed. Results indicated that the histologically confirmed CRC condition led to a downregulation of the WNT/ß-catenin pathway, along with alterations in oncogenic and tumor suppressor gene expression. However, OBG significantly modulated these effects, with the 3% OBG showing a more pronounced impact. Furthermore, CRC rats exhibited elevated levels of oxidative stress and antioxidant enzyme activity in the blood, along with decreased white blood cell and lymphocyte counts. Consumption of OBG at any dose normalized these parameters. The minimal effect of OBG in the physiological intestine and the high activity in the pathological condition suggest that OBG is both safe and effective in early-stage CRC.


Assuntos
Avena , Suplementos Nutricionais , Estresse Oxidativo , Ratos Sprague-Dawley , beta-Glucanas , Animais , Masculino , beta-Glucanas/farmacologia , beta-Glucanas/administração & dosagem , Avena/química , Ratos , Estresse Oxidativo/efeitos dos fármacos , Neoplasias do Colo/prevenção & controle , Anticarcinógenos/farmacologia , Azoximetano , Via de Sinalização Wnt/efeitos dos fármacos , Modelos Animais de Doenças , Ração Animal , Colo/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Neoplasias Colorretais/prevenção & controle , Antioxidantes/farmacologia
4.
Nutrients ; 16(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542669

RESUMO

Isothiocyanates are biologically active products resulting from the hydrolysis of glucosinolates predominantly present in cruciferous vegetables belonging to the Brassicaceae family. Numerous studies have demonstrated the diverse bioactivities of various isothiocyanates, encompassing anticarcinogenic, anti-inflammatory, and antioxidative properties. Nature harbors distinct isothiocyanate precursors, glucosinolates such as glucoraphanin and gluconastrin, each characterized by unique structures, physical properties, and pharmacological potentials. This comprehensive review aims to consolidate the current understanding of Moringa isothiocyanates, mainly 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate), comparing this compound with other well-studied isothiocyanates such as sulforaphane and phenyl ethyl isothiocyanates. The focus is directed toward elucidating differences and similarities in the efficacy of these compounds as agents with anticancer, anti-inflammatory, and antioxidative properties.


Assuntos
Anticarcinógenos , Brassicaceae , Glucosinolatos/farmacologia , Brassicaceae/química , Isotiocianatos/farmacologia , Antioxidantes/farmacologia , Anti-Inflamatórios , Anticarcinógenos/farmacologia
5.
Toxicol Appl Pharmacol ; 485: 116916, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537874

RESUMO

This study aims to explore the impact and underlying mechanism of sulforaphane (SFN) intervention on the migration and invasion of lung adenocarcinoma induced by 7, 8-dihydroxy-9, 10-epoxy-benzo (a) pyrene (BPDE). Human lung adenocarcinoma A549 cells were exposed to varying concentrations of BPDE (0.25, 0.50, and 1.00 µM) and subsequently treated with 5 µM SFN. Cell viability was determined using CCK8 assay, while migration and invasion were assessed using Transwell assays. Lentivirus transfection was employed to establish NLRP12 overexpressing A549 cells. ELISA was utilized to quantify IL-33, CXCL12, and CXCL13 levels in the supernatant, while quantitative real-time PCR (qRT-PCR) and Western Blot were used to analyze the expression of NLRP12 and key factors associated with canonical and non-canonical NF-κB pathways. Results indicated an increase in migratory and invasive capabilities, concurrent with heightened expression of IL-33, CXCL12, CXCL13, and factors associated with both canonical and non-canonical NF-κB pathways. Moreover, mRNA and protein levels of NLRP12 were decreased in BPDE-stimulated A549 cells. Subsequent SFN intervention attenuated BPDE-induced migration and invasion of A549 cells. Lentivirus-mediated NLRP12 overexpression not only reversed the observed phenotype in BPDE-induced cells but also led to a reduction in the expression of critical factors associated with both canonical and non-canonical NF-κB pathways. Collectively, we found that SFN could inhibit BPDE-induced migration and invasion of A549 cells by upregulating NLRP12, thereby influencing both canonical and non-canonical NF-κB pathways.


Assuntos
Adenocarcinoma de Pulmão , Movimento Celular , Isotiocianatos , Neoplasias Pulmonares , Invasividade Neoplásica , Sulfóxidos , Humanos , Isotiocianatos/farmacologia , Sulfóxidos/farmacologia , Movimento Celular/efeitos dos fármacos , Células A549 , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Anticarcinógenos/farmacologia , NF-kappa B/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
6.
Bol. latinoam. Caribe plantas med. aromát ; 23(2): 214-228, mar. 2024. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1552134

RESUMO

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.


Assuntos
Anticarcinógenos , Passiflora , Passifloraceae/metabolismo , Triglicerídeos/fisiologia , Extratos Vegetais/farmacologia , Colesterol/fisiologia , Frutas
7.
Med Oncol ; 41(4): 82, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416317

RESUMO

Metformin is a drug that is widely used in the treatment of type-2 diabetes and its anticarcinogenic effect has been detected in many studies since the 2000s. Metformin has a short half-life and poor biocompatibility, which limits the activity of the drug. As a solution to this situation, our study aimed to increase the anticarcinogenic effects and reduce the side effects of metformin in colon cancer by liposomal encapsulation. For this purpose, in our study, liposome production was carried out using the thin film hydration method. The amount of metformin loaded in liposomes was determined by a standard absorbance curve at 237 nm. Size distributions and membrane zeta potentials of the liposomes were evaluated with Malvern Zetasizer ZS90. Transmission electron microscopy was performed by staining the liposomes negatively with uranyl acetate. Cultured HT-29 cells were treated with liposomal metformin or free metformin at concentrations of 0, 10, 20, and 40 mM for 24 and 48 h. At the end of the treatment period, cell viability was evaluated by CellTiter-Glo luminescent cell viability test. The anticarcinogenic effects of liposomal and free metformin on HT-29 cells were compared. As a result, liposome encapsulated metformin treatment for 24 h was more effective on HT-29 cells at 20- and 40-mM concentrations causing significantly greater decrease in the IC-50 dose compared to the free metformin. The result suggests that liposomal encapsulated metformin may offer a promising approach to increase the efficacy of the drug in the treatment of colon cancer.


Assuntos
Anticarcinógenos , Neoplasias do Colo , Metformina , Humanos , Metformina/farmacologia , Lipossomos , Resultado do Tratamento , Neoplasias do Colo/tratamento farmacológico
8.
Nutrients ; 16(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276538

RESUMO

Exposure to B[a]P, the most characterized polycyclic aromatic hydrocarbon, significantly increases breast cancer risk. Our lab has previously reported that diallyl trisulfide (DATS), a garlic organosulfur compound (OSC) with chemopreventive and cell cycle arrest properties, reduces lipid peroxides and DNA damage in normal breast epithelial (MCF-10A) cells. In this study, we evaluated the ability of DATS to block the B[a]P-induced initiation of carcinogenesis in MCF-10A cells by examining changes in proliferation, clonogenic formation, reactive oxygen species (ROS) formation, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and protein expression of ARNT/HIF-1ß, CYP1A1, and DNA POLß. The study results indicate that B[a]P increased proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing the protein expression of ARNT/HIF-1ß and CYP1A1 compared to the control. Conversely, DATS/B[a]P co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, and 8-OHdG levels compared to B[a]P alone. Treatment with DATS significantly inhibited (p < 0.0001) AhR expression, implicated in the development and progression of breast cancer. The CoTx also attenuated all the above-mentioned B[a]P-induced changes in protein expression. At the same time, it increased DNA POLß protein expression, which indicates increased DNA repair, thus causing a chemopreventive effect. These results provide evidence for the chemopreventive effects of DATS in breast cancer prevention.


Assuntos
Compostos Alílicos , Anticarcinógenos , Neoplasias da Mama , Alho , Lesões Pré-Cancerosas , Humanos , Feminino , Alho/metabolismo , Antioxidantes/farmacologia , Benzo(a)pireno/toxicidade , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Apoptose , Sulfetos/farmacologia , Células Epiteliais/metabolismo , Anticarcinógenos/farmacologia , Reparo do DNA , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , DNA
9.
Toxicol Mech Methods ; 34(5): 507-516, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38221767

RESUMO

This study aimed to examine the expression and biological functions of ACTL6A in glioma cells (U251), the effects of sulforaphane on the growth of U251 cells and the involvement of the ACTL6A/PGK1 pathway in those effects. The U251 cell line was transfected with ACTL6A over-expression plasmids to upregulate the protein, or with ACTL6A inhibitor to underexpress it, then treated with different concentrations of sulforaphane. Cell viability, proliferation, and apoptosis were assessed using standard assays, and levels of mRNAs encoding ACTL6A, PGK1, cyclin D1, Myc, Bax or Bcl-2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). ACTL6A and PGK1 were expressed at higher levels in glioma cell lines than in normal HEB cells. ACTL6A overexpression upregulated PGK1, whereas ACTL6A inhibition had the opposite effect. ACTL6A overexpression induced proliferation, whereas its inhibition repressed proliferation, enhanced apoptosis, and halted the cell cycle. Moreover, sulforaphane suppressed the growth of U251 cells by inactivating the ACTL6A/PGK1 axis. ACTL6A acts via PGK1 to play a critical role in glioma cell survival and proliferation, and sulforaphane targets it to inhibit glioma.


Assuntos
Anticarcinógenos , Apoptose , Proliferação de Células , Glioma , Isotiocianatos , Fosfoglicerato Quinase , Sulfóxidos , Humanos , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/patologia , Glioma/metabolismo , Glioma/tratamento farmacológico , Glioma/genética , Isotiocianatos/farmacologia , Fosfoglicerato Quinase/genética , Fosfoglicerato Quinase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Anticarcinógenos/farmacologia
10.
Cancer Metastasis Rev ; 43(1): 55-85, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37507626

RESUMO

Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy as monotherapy can lead to significant side effects and chemoresistance that can be linked to several resistance-activating biological processes, including an increase in inflammation, cellular plasticity, multidrug resistance (MDR), inhibition of the sentinel gene p53, and apoptosis. As a consequence, tumor cells can escape the effectiveness of chemotherapeutic agents. This underscores the need for cross-target therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways and sensitize cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to conventional medications for the synergistic treatment of CRC. Resveratrol, a natural polyphenolic phytoalexin found in various fruits and vegetables such as peanuts, berries, and red grapes, is one of the most effective natural chemopreventive agents. Abundant in vitro and in vivo studies have shown that resveratrol, in interaction with standard drugs, is an effective chemosensitizer for CRC cells to chemotherapeutic agents and thus prevents drug resistance by modulating multiple pathways, including transcription factors, epithelial-to-mesenchymal transition-plasticity, proliferation, metastasis, angiogenesis, cell cycle, and apoptosis. The ability of resveratrol to modify multiple subcellular pathways that may suppress cancer cell plasticity and reversal of chemoresistance are critical parameters for understanding its anti-cancer effects. In this review, we focus on the chemosensitizing properties of resveratrol in CRC and, thus, its potential importance as an additive to ongoing treatments.


Assuntos
Anticarcinógenos , Neoplasias Colorretais , Estilbenos , Humanos , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Transdução de Sinais , Fatores de Transcrição , Anticarcinógenos/farmacologia , Neoplasias Colorretais/patologia , Estilbenos/farmacologia , Estilbenos/uso terapêutico
11.
Phytother Res ; 38(1): 331-348, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37882581

RESUMO

The isothiocyanates (ITCs) derived from the precursor glucosinolate molecules present in Brassica vegetables are bioactive organo-sulfur compounds with numerous pharmacologically important properties such as antioxidant, antiinflammatory, antimicrobial, and anticancer. Over the years, ITCs have been the focus of several research investigations associated with cancer treatment. Due to their potent chemo-preventive action, ITCs have been considered to be promising therapeutics for cancer therapy in place of the already existing conventional anticancer drugs. However, their wide spread use at the clinical stage is greatly restricted due to several factors such as low solubility in an aqueous medium, low bioavailability, low stability, and hormetic effect. To overcome these hindrances, nanotechnology can be exploited to develop nano-scale delivery systems that have the potential to enhance stability, and bioavailability and minimize the hermetic effect of ITCs.


Assuntos
Anticarcinógenos , Antineoplásicos , Brassica , Isotiocianatos/farmacologia , Verduras , Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico , Antineoplásicos/farmacologia
12.
Int J Biol Macromol ; 254(Pt 1): 127718, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37918594

RESUMO

In this study, the nano-assemblies of bovine casein hydrolyzed peptides (HP) modified by fatty acids with various alkyl chain lengths (C8, C10, C12 and C14) were synthesized. The physicochemical properties of HP-C8-HP-C14 nano-assemblies were characterized using spectra, laser particle size analyzer, contact angle meter, scanning electron microscope (SEM) and cryo-transmission electron microscope (Cryo-TEM). HP-C8 and HP-C10 self-assembled into a hollow cube cage with an average size of ~500 nm, and the assembly of HP-C12 showed a flower-shaped morphology with more dispersed behavior, and droplet size was observed as ~20 nm. The in vitro cytotoxicity against human breast cancer cells MCF-7 was tested using CCK-8 assay and flow cytometry analysis. HP-C12 showed the highest cytotoxicity for MCF-7 cells with an inhibition rate of 66.03 % ± 0.35 % with an IC50 value of 7.4 µM among HP-Cn. HP-C8, HP-C10 and HP-C12 significantly affected on the migration, invasion and apoptosis of MCF-7 cells. The apoptosis mechanism may depend on the upregulation of anti-apoptotic protein Bcl-2 as well as pro-apoptotic proteins Bax and caspase-8. The dead MCF-7 cells were analyzed with UHPLC-MS/MS using untargeted metabolomics, revealing key metabolic pathways.


Assuntos
Anticarcinógenos , Ácidos Graxos , Animais , Bovinos , Humanos , Ácidos Graxos/química , Anticarcinógenos/farmacologia , Caseínas/farmacologia , Espectrometria de Massas em Tandem , Apoptose , Células MCF-7
13.
Nutrients ; 15(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38004214

RESUMO

Okra flowers are a good source of polysaccharides and flavonoids, with biological activities of anti-inflammatory action and modulation of the gut microbiota. Previously, we reported that flavonoid-rich extracts from okra flowers (AFE) presented effective anti-colorectal cancer (CRC) activity in CRC cells as well as xenograft models, but their role in colitis-associated cancer (CAC) is unidentified. In this study, we aimed to evaluate the effects of AFE and APE (polysaccharides extracted from okra flowers) on the CAC symptoms of azoxymethane (AOM)/dextran sodium sulfate (DSS)-intervened mice. The results showed that APE and AFE exert potent efficacy in inhibiting colitis and colorectal tumorigenesis stimulated by AOM/DSS, characterized by decreased colonic shortening, DAI score, and tumor numbers. Compared with the control group, APE/AFE alleviated the microbiota dysbiosis driven by AOM/DSS. In addition, AFE elicited its anticancer activity through regulation of NFκB/IL-6/Stat3, JAK2/Stat3, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in AOM/DSS mice, which was consistent with a vitro model of CT26 cells, while APE treatment exhibited anticancer activity through regulation of Nrf2/IL-6, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in the AOM/DSS mouse model. Collectively, our studies revealed, for the first time, that flavonoids and polysaccharides from okra flowers possess the ability to attenuate colitis and colorectal tumorigenesis, with them having great potential to become promising candidates against CRC.


Assuntos
Abelmoschus , Anticarcinógenos , Neoplasias Associadas a Colite , Colite , Neoplasias Colorretais , Hominidae , Humanos , Camundongos , Animais , Flavonoides/efeitos adversos , Sulfato de Dextrana/efeitos adversos , Interleucina-6 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , beta Catenina , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Azoximetano , Carcinogênese , Transformação Celular Neoplásica , Anticarcinógenos/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Neoplasias Colorretais/patologia
14.
Sci Rep ; 13(1): 17234, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821474

RESUMO

Dietary components have recently received rapidly expanding attention for their potential to halt or reverse the development of many oxidative stress-mediated diseases after exposure to environmental toxicants. 7, 12 dimethylbenz(a)anthracene (DMBA) is one of the most common environmental pollutants. The present study aimed to evaluate the chemo-preventive effects of broccoli as a nutritional component against DMBA intoxication in rats. A daily dose of aqueous (1 ml/rat) and methanolic (150 mg/kg) broccoli extracts, respectively, was given to 50-day-old female rats for 26 successive weeks after carcinogen intoxication with a single dose of 20 mg/ml of DMBA. DMBA intoxication resulted in a redox imbalance (a decreased GSH level and an increased MDA level) and increased DNA fragmentation in the liver, kidney, and brain. Besides, it affected the level of expression of the bcl2 gene in the liver, kidney, and brain tissue but didn't affect cfos gene expression accompanied by histopathological changes. The aqueous and methanolic broccoli extract supplements ameliorated the adverse effects by increasing the level of GSH, decreasing the MDA level, and reducing DNA fragmentation. Besides, broccoli extracts decreased the expression of bcl2 in the liver and brain and up-regulated bcl2 expression in the kidney, accompanied by lowering NF-κß 65 expression in the liver and brain and γ-catenin expression in the liver and kidney. In conclusion, broccoli as a dietary component had a strong chemoprotective effect against oxidative stress, DNA damage, and genotoxicity induced by DMBA intoxication in rats.


Assuntos
Anticarcinógenos , Brassica , Ratos , Feminino , Animais , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Brassica/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2 , Suplementos Nutricionais , Antracenos
15.
Pharm Res ; 40(11): 2699-2714, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37726406

RESUMO

Since ancient times, dietary phytochemicals are known for their medicinal properties. They are broadly classified into polyphenols, terpenoids, alkaloids, phytosterols, and organosulfur compounds. Currently, there is considerable interest in their potential health effects against various diseases, including lung cancer. Lung cancer is the leading cause of cancer deaths with an average of five-year survival rate of lung cancer patients limited to just 14%. Identifying potential early molecular biomarkers of pre-malignant lung cancer cells may provide a strong basis to develop early cancer detection and interception methods. In this review, we will discuss molecular changes, including genetic alterations, inflammation, signal transduction pathways, redox imbalance, epigenetic and proteomic signatures associated with initiation and progression of lung carcinoma. We will also highlight molecular targets of phytochemicals during lung cancer development. These targets mainly consist of cellular signaling pathways, epigenetic regulators and metabolic reprogramming. With growing interest in natural products research, translation of these compounds into new cancer prevention approaches to medical care will be urgently needed. In this context, we will also discuss the overall pharmacokinetic challenges of phytochemicals in translating to humans. Lastly, we will discuss clinical trials of phytochemicals in lung cancer patients.


Assuntos
Anticarcinógenos , Neoplasias Pulmonares , Neoplasias , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/patologia , Anticarcinógenos/uso terapêutico , Dieta , Proteômica , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Biomarcadores
16.
Phytother Res ; 37(11): 5159-5192, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37668281

RESUMO

Flavonoids are natural polyphenolic compounds considered safe, pleiotropic, and readily available molecules. It is widely distributed in various food products such as fruits and vegetables and beverages such as green tea, wine, and coca-based products. Many studies have reported the anticancer potential of flavonoids against different types of cancers, including solid tumors. The chemopreventive effect of flavonoids is attributed to various mechanisms, including modulation of autophagy, induction of cell cycle arrest, apoptosis, and antioxidant defense. Despite of significant anticancer activity of flavonoids, their clinical translation is limited due to their poor biopharmaceutical attributes (such as low aqueous solubility, limited permeability across the biological membranes (intestinal and blood-brain barrier), and stability issue in biological systems). A nanoparticulate system is an approach that is widely utilized to improve the biopharmaceutical performance and therapeutic efficacy of phytopharmaceuticals. The present review discusses the significant anticancer potential of promising flavonoids in different cancers and the utilization of nanoparticulate systems to improve their nanoantioxidant activity further to enhance the anticancer activity of loaded promising flavonoids. Although, various plant-derived secondary metabolites including flavonoids have been recommended for treating cancer, further vigilant research is warranted to prove their translational values.


Assuntos
Anticarcinógenos , Produtos Biológicos , Neoplasias , Humanos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Flavonoides/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Anticarcinógenos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Produtos Biológicos/uso terapêutico
17.
Mol Biol Rep ; 50(11): 9099-9105, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37747682

RESUMO

BACKGROUND: Oleuropein (OLE), the main phenolic compound of the olive fruit and leaves, has many heathful effects. Gastric cancer is the most fatal malignancy in many parts of the world and it is generally related to harmful dietetic factors. The anticarcinogenic role of OLE in gastric cancer has not been studied sufficiently yet. In this study, we aimed to research the cytotoxic, genotoxic and apoptotic effects of OLE on gastric adenocancer (AGS) cells in vitro. METHODS AND RESULTS: A standard cell line derived from gastric adeno cancer (AGS) cells was employed, and its performance following a 24-hour exposure to OLE at various doses was examined. The ATP cell viability assay, 2',7'-dichlorodihydrofluorescein-diacetate assay (H2DCF-DA) and alkaline single cell gel electrophoresis assay (Comet Assay) were used to study the cytotoxicity, production of reactive oxygen species (ROS) and genotoxicity respectively. The induction of apoptosis was discovered using flow cytometry. OLE reduced AGS cells viability about 60% at maximum concentration (500 µmol/L) and also resulted in approximately 100% DNA damage and about 40% apoptosis with necrosis in AGS cells depending on the increased doses. Cell viability was also significantly decreased in relation to increased intracellular reactive oxygen species (ROS) levels (p < 0.05 - 0.001). CONCLUSIONS: Oleuropein has shown significant anticarcinogen effects against gastric adenocancer (AGS) cells in vitro. Oleuropein, a nutrient rich in olive and olive oil, seems to be both protective and therapeutic against gastric cancer and may be a new chemotherapeutic agent in the future.


Assuntos
Anticarcinógenos , Neoplasias Gástricas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Linhagem Celular
18.
Biochem Biophys Res Commun ; 671: 132-139, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37302286

RESUMO

Pancreatic cancer (PC) continues to be devastating due to its highly malignant nature and poor prognosis. The limited benefits of the chemotherapeutic drugs and increasing resistance pose a critical challenge to overcome and warrant investigations for new therapeutic agents. Several preclinical and clinical studies have suggested a possible role of the androgen receptor (AR) signaling pathway in PC development and progression. Nevertheless, the studies are limited and inconclusive in explaining the molecular link between AR signaling and PC. Selective androgen receptor modulators (SARMs) are small molecule drugs with high affinity for the androgen receptor. SARMs elicit selective anabolic activities while abrogating undesired androgenic side effects. There is no study focusing on the utility of SARMs as inhibitors of PC. Here, we report the first study evaluating the possible anti-carcinogenic influences of andarine, a member of the SARMs, on PC. The data we presented here has illustrated that andarine repressed PC cell growth and proliferation via cell cycle arrest at G0/G1 phase. Gene expression analysis revealed that it downregulates CDKN1A expression level accordingly. Furthermore, we established that the anti-carcinogenic activity of andarine is not mediated by the PI3K/AKT/mTOR signaling pathway, a crucial regulator of cell survival. Our findings suggest that andarine might be considered as a prospective drug for PC.


Assuntos
Anticarcinógenos , Receptores Androgênicos , Receptores Androgênicos/metabolismo , Anticarcinógenos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Androgênios/farmacologia , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Fase G1 , Linhagem Celular Tumoral
19.
Asian Pac J Cancer Prev ; 24(5): 1695-1700, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37247290

RESUMO

OBJECTIVE: To evaluate the anti-carcinogenic effect of Centella Asiatica on to evaluate the  Anti-Carcinogenic Effect of Centella Asiatica on Oral Cancer Cell Line oral cancer cell line. MATERIALS AND METHODS:  Oral Cancer cell line and normal oral keratinocyte cell line were procured.Centella asiatica extract was prepared. The cells were then subjected to the test herbal specimens -Centella asiatica extract in succeeding concentrations of 25 µg/ml, 50 µg/ml, 100 µg/ml at time intervals of 24,48 and 72 hours. Cisplatin (2 µg/ml, 4 µg/ml, 6 µg/ml, 8 µg/ml) was used as a positive control. This experiment was done in triplets. RESULTS: The study revealed that the p values were less than 0.05 at concentration 12.5µg/ml, 25µg/ml, 50 µg/ml,100 µg/ml and time period of 24hrs,48hrs,72hrs, thus implying that at these concentrations and time period, the obtained data were statistically significant, thus indicating that there is a statistically significantly decreases in the viable cells as the concentration of the drug as a time period increases The results reveals that  centella asiatica possess potential effect of anti-carcinogenic, effect when compared to positive control (Cisplatin). CONCLUSION: The current study reveals that Centella asiatica has an potential anti-carcinogenic effect on oral cancer cell line. So this can be used to treat oral cancer with minimal crippling as compared with allopathic drugs.


Assuntos
Anticarcinógenos , Centella , Neoplasias Bucais , Triterpenos , Humanos , Cisplatino/farmacologia , Triterpenos/farmacologia , Extratos Vegetais/farmacologia , Linhagem Celular , Neoplasias Bucais/tratamento farmacológico
20.
Phytomedicine ; 116: 154850, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37187036

RESUMO

BACKGROUND: Lung cancer is one of the leading causes of malignancy in the world. Several therapeutical and chemopreventive approaches have been practised to mitigate the disease. The use of phytopigments including carotenoids is a well-known approach. However, some of the prominent clinical trials interrogated the efficacy of carotenoids in lung cancer prevention. METHODS: A elaborate literature survey have been performed investigating in vitro, in vivo, and clinical studies reported on the administration of carotenoids for chemoprevention and chemotherapy. RESULTS: Tobacco consumption, genetic factors, dietary patterns, occupational carcinogens, lung diseases, infection, and sex disparities are some of the prominent factors leading to lung cancer. Significant evidence has been found underlining the efficiency of carotenoids in alleviating cancer. In vitro studies have proven that carotenoids act through PI3K/ AKT/mTOR, ERK-MAPK pathways and induce apoptosis through PPAR, IFNs, RAR, which are p53 intermediators in lung cancer signaling. Animal models and cell lines studies showed promising results, while the outcomes of clinical trials are contradictory and require further verification. CONCLUSION: The carotenoids exert chemotherapeutic and chemopreventive effects on lung tumors which has been evidenced in numerous investigations. However, further analyses are necessary to the answer the uncertainties raised by several clinical trials.


Assuntos
Anticarcinógenos , Neoplasias Pulmonares , Animais , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Quimioprevenção/métodos , Anticarcinógenos/farmacologia , Antioxidantes/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...