RESUMEN
Cancer is a complicated and ever-evolving disease that remains a significant global cause of disease and mortality. Its complexity, which is evident at the genetic and phenotypic levels, contributes to its diversity and resistance to treatment. Numerous scientific investigations on human and animal models demonstrate the potential of phytochemicals in cancer prevention. Coffee has been shown to possess potent anti-carcinogenic properties, and studies have documented the consumption of coffee as a beverage reduces the risk of cancer occurrence. The major secondary metabolites of coffee, named caffeine and chlorogenic acid, have been linked to anti-inflammatory and antineoplastic effects through various signaling. In light of this, this review article provides a comprehensive analysis based on studies in anticancer effects of coffee, chlorogenic acid, and caffeine published between 2010 and 2023, sourced from Scopus, Pubmed, and Google Scholar databases. We summarize recent advances and scientific evidence on the association of phytochemicals found in coffee with a special emphasis on their biological activities against cancer and their molecular mechanism deemed potential to be used as a novel therapeutic target for cancer prevention and therapy.
Asunto(s)
Cafeína , Ácido Clorogénico , Café , Neoplasias , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Humanos , Cafeína/farmacología , Cafeína/química , Café/química , Neoplasias/prevención & control , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Fitoquímicos/farmacología , Fitoquímicos/química , Fitoquímicos/uso terapéutico , Quimioprevención , Anticarcinógenos/farmacología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/químicaRESUMEN
Triple-negative breast cancer (TNBC) represents aggressive phenotype with limited treatment options due to the lack of drug targets. Natural compounds are extensively studied regarding their potential to alter the efficacy of cancer treatment Among them sulforaphane - an isothiocyanate of natural origin, was shown to be a hormetic compound, that may exert divergent effects: cytoprotective or cytotoxic depending on its concentrations. Thus, the aim of this study was to determine the effect of its low, dietary concentrations on the proliferation and migration of the TNBC cells in the in vivo and in vitro 2D and 3D model. Results of the in vivo experiment showed up to 31% tumor growth inhibition after sulforaphane treatment associated with lowered proliferating potential of cancer cells, reduced areas of necrosis, and changed immune cell type infiltration, showing less malignant type of tumor in contrast to the non-treated group. Also, the study revealed that sulforaphane decreased the number of lung metastases. The in vitro study confirmed that SFN inhibited cell migration, but only in cells derived from 3D spheroids, not from 2D in vitro cultures. The results show a specific role of sulforaphane in the case of cells released from the TNBC primary tumor and its environment.
Asunto(s)
Movimiento Celular , Proliferación Celular , Isotiocianatos , Sulfóxidos , Neoplasias de la Mama Triple Negativas , Isotiocianatos/farmacología , Isotiocianatos/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Sulfóxidos/farmacología , Femenino , Humanos , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Animales , Proliferación Celular/efectos de los fármacos , Ratones , Anticarcinógenos/farmacología , Anticarcinógenos/administración & dosificación , Anticarcinógenos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The incidence of breast cancer is increasing annually, making it a major health threat for women. Chemoprevention using natural, dietary, or synthetic products has emerged as a promising approach to address this growing burden. Atractylenolide-III (AT-III), a sesquiterpenoid present in various medicinal herbs, has demonstrated potential therapeutic effects against several diseases, including tumors, nonalcoholic fatty liver disease, and cerebral ischemic injury. However, its impact on breast cancer chemoprevention remains unexplored. In this study, we used an N-methyl-N-nitrosourea (NMU)-induced rat breast cancer model and 17ß-estradiol (E2)-treated MCF-10A cells to evaluate the chemopreventive potential of AT-III on mammary tumorigenesis. AT-III inhibited mammary tumor progression, evidenced by reduced tumor volume and multiplicity, prolonged tumor latency, and the reversal of NMU-induced weight loss. Furthermore, AT-III suppressed NMU-induced inflammation and oxidative stress through the Nrf2/ARE pathway in breast cancer tissues. In vitro, AT-III effectively suppressed E2-induced anchorage-independent growth and cell migration in MCF-10A cells. Nrf2 knockdown attenuated the protective effects of AT-III, highlighting the pivotal role of Nrf2 in AT-III-mediated suppression of tumorigenesis. The mechanism involves the induction of Nrf2 expression by AT-III through the autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Overall, the results of this study indicate that AT-III is a promising candidate for breast cancer chemoprevention and provide valuable insights into its molecular interactions and signaling pathways.
Asunto(s)
Autofagia , Proteína 1 Asociada A ECH Tipo Kelch , Lactonas , Factor 2 Relacionado con NF-E2 , Sesquiterpenos , Transducción de Señal , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Sesquiterpenos/farmacología , Femenino , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Lactonas/farmacología , Autofagia/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratas , Humanos , Línea Celular Tumoral , Ratas Sprague-Dawley , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/patología , Neoplasias Mamarias Experimentales/prevención & control , Neoplasias Mamarias Experimentales/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Metilnitrosourea/toxicidad , Carcinogénesis/efectos de los fármacos , Anticarcinógenos/farmacología , Estradiol/farmacologíaRESUMEN
Despite recent advances in tumor diagnosis and treatment technologies, the number of cancer cases and deaths worldwide continues to increase yearly, creating an urgent need to find new methods to prevent or treat cancer. Sulforaphane (SFN), as a member of the isothiocyanates (ITCs) family, which is the hydrolysis product of glucosinolates (GLs), has been shown to have significant preventive and therapeutic cancer effects in different human cancers. Early studies have shown that SFN scavenges oxygen radicals by increasing cellular defenses against oxidative damage, mainly through the induction of phase II detoxification enzymes by nuclear factor erythroid 2-related factor 2 (Nrf2). More and more studies have shown that the anticancer mechanism of SFN also includes induction of apoptotic pathway in tumor cells, inhibition of cell cycle progression, and suppression of tumor stem cells. Therefore, the application of SFN is expected to be a necessary new approach to treating cancer. In this paper, we review the multiple molecular mechanisms of SFN in cancer prevention and treatment in recent years, which can provide a new vision for cancer treatment.
Asunto(s)
Anticarcinógenos , Isotiocianatos , Neoplasias , Sulfóxidos , Isotiocianatos/farmacología , Isotiocianatos/uso terapéutico , Sulfóxidos/farmacología , Sulfóxidos/uso terapéutico , Humanos , Neoplasias/prevención & control , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose-dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.
Asunto(s)
Bexaroteno , Dislipidemias , Hipotiroidismo , Humanos , Bexaroteno/efectos adversos , Hipotiroidismo/inducido químicamente , Hipotiroidismo/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Dislipidemias/inducido químicamente , Japón/epidemiología , Tiroxina/sangre , Triglicéridos/sangre , Adulto , Tetrahidronaftalenos/efectos adversos , Tetrahidronaftalenos/uso terapéutico , Anciano de 80 o más Años , Anticarcinógenos/uso terapéutico , Anticarcinógenos/efectos adversos , Hipertrigliceridemia/inducido químicamenteRESUMEN
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.
Asunto(s)
Neoplasias de la Mama , Epigénesis Genética , Microbioma Gastrointestinal , Isotiocianatos , Sulfóxidos , Witanólidos , Isotiocianatos/farmacología , Animales , Witanólidos/farmacología , Sulfóxidos/farmacología , Femenino , Ratones , Epigénesis Genética/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/prevención & control , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Transgénicos , Extractos Vegetales/farmacología , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Humanos , Brassica/química , Histona Desacetilasa 1/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Anticarcinógenos/farmacologíaRESUMEN
The vitamin E family contains α-tocopherol (αT), ßT, γT, and δT and α-tocotrienol (TE), ßTE, γTE, and δTE. Research has revealed distinct roles of these vitamin E forms in prostate cancer (PCa). The ATBC trial showed that αT at a modest dose significantly decreased PCa mortality among heavy smokers. However, other randomized controlled trials including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicate that supplementation of high-dose αT (≥400 IU) does not prevent PCa among nonsmokers. Preclinical cell and animal studies also do not support chemopreventive roles of high-dose αT and offer explanations for increased incidence of early-stage PCa reported in the SELECT. In contrast, accumulating animal studies have demonstrated that γT, δT, γTE, and δTE appear to be effective for preventing early-stage PCa from progression to adenocarcinoma in various PCa models. Existing evidence also support therapeutic roles of γTE and its related combinations against advanced PCa. Mechanistic and cell-based studies show that different forms of vitamin E display varied efficacy, that is, δTE ≥ γTE > δT ≥ γT >> αT, in inhibiting cancer hallmarks and enabling characteristics, including uncontrolled cell proliferation, angiogenesis, and inflammation possibly via blocking 5-lipoxygenase, nuclear factor κB, hypoxia-inducible factor-1α, modulating sphingolipids, and targeting PCa stem cells. Overall, existing evidence suggests that modest αT supplement may be beneficial to smokers and γT, δT, γTE, and δTE are promising agents for PCa prevention for modest-risk to relatively high-risk population. Despite encouraging preclinical evidence, clinical research testing γT, δT, γTE, and δTE for PCa prevention is sparse and should be considered.
Asunto(s)
Neoplasias de la Próstata , Tocoferoles , Tocotrienoles , Masculino , Humanos , Neoplasias de la Próstata/prevención & control , Tocotrienoles/farmacología , Tocotrienoles/uso terapéutico , Tocoferoles/farmacología , Tocoferoles/uso terapéutico , Animales , Suplementos Dietéticos , Quimioprevención/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina E/farmacología , Vitamina E/uso terapéutico , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéuticoRESUMEN
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.
Asunto(s)
Humanos , Anticarcinógenos , Moringa , Inhibidores Enzimáticos , alfa-GlucosidasasRESUMEN
T agetes patula , known as French Marigold, belongs to the family Asteraceae. Human papillomavirus infection is considered one of the causes of cervical cancer. This study assessed the cytotoxic activity and intracellular oxidative capacity of compounds isolated from extract of T. patula flowers as anti - cancer cervical agents. Fraction F6 of n - butanol extract was subjected to column chromatography and HPLC - ESI - MS. The isolated compo unds of T. patula were used to examine cytotoxic activity and the production of total reactive oxygen species in SiHa and HeLa cells; the cells were also characterized using scanning electron microscopy. Patulitrin was cytotoxic to SiHa and HeLa cells. An increase in ROS production was observed at different times of treatment of cells with patuletin and patulitrin. Scanning electron microscopy showed morphological changes in SiHa and HeLa cells. Thus, compounds isolated from T. patula have great treatment p otential against cervical cancer.
Tagetes patula , conocida como cempasúchil francés, pertenece a la familia Asteraceae. La infección por el virus del papiloma humano se considera una de las causas del cáncer cervical. En este estudio, se evaluó la actividad citotóxica y la capacidad oxidativa intracelular de los compuestos aislados del extracto de las flores de T. patula como agentes anticancerígenos cervicales. La fracción F6 del ext racto de n - butanol se sometió a cromatografía en columna y HPLC - ESI - MS. Los compuestos aislados de T. patula se utilizaron para examinar la actividad citotóxica y la producción total de especies reactivas de oxígeno en las células SiHa y HeLa; las células también se caracterizaron mediante microscopía electrónica de barrido. Patulitrina resultó citotóxica para las células SiHa y HeLa. Se observó un aumento en la producción de ROS en diferentes momentos del tratamiento de las células con patuletina y patulit rina. La microscopía electrónica de barrido mostró cambios morfológicos en las células SiHa y HeLa. Por lo tanto, los compuestos aislados de T. patula tienen un gran potencial de tratamiento contra el cáncer cervical.
Asunto(s)
Humanos , Flavonoides/aislamiento & purificación , Extractos Vegetales/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Anticarcinógenos/química , Tagetes/química , Extractos Vegetales/administración & dosificación , Microscopía Electrónica de Rastreo , Cromatografía Líquida de Alta Presión , Anticarcinógenos/administración & dosificación , Línea Celular Tumoral/efectos de los fármacosRESUMEN
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.
Asunto(s)
Avena , Suplementos Dietéticos , Estrés Oxidativo , Ratas Sprague-Dawley , beta-Glucanos , Animales , Masculino , beta-Glucanos/farmacología , beta-Glucanos/administración & dosificación , Avena/química , Ratas , Estrés Oxidativo/efectos de los fármacos , Neoplasias del Colon/prevención & control , Anticarcinógenos/farmacología , Azoximetano , Vía de Señalización Wnt/efectos de los fármacos , Modelos Animales de Enfermedad , Alimentación Animal , Colon/patología , Colon/efectos de los fármacos , Colon/metabolismo , Neoplasias Colorrectales/prevención & control , Antioxidantes/farmacologíaRESUMEN
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.
Asunto(s)
Anticarcinógenos , Brassicaceae , Glucosinolatos/farmacología , Brassicaceae/química , Isotiocianatos/farmacología , Antioxidantes/farmacología , Antiinflamatorios , Anticarcinógenos/farmacologíaRESUMEN
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.
Asunto(s)
Adenocarcinoma del Pulmón , Movimiento Celular , Isotiocianatos , Neoplasias Pulmonares , Invasividad Neoplásica , Sulfóxidos , Humanos , Isotiocianatos/farmacología , Sulfóxidos/farmacología , Movimiento Celular/efectos de los fármacos , Células A549 , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/toxicidad , Anticarcinógenos/farmacología , FN-kappa B/metabolismo , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
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.
Asunto(s)
Anticarcinógenos , Passiflora , Passifloraceae/metabolismo , Triglicéridos/fisiología , Extractos Vegetales/farmacología , Colesterol/fisiología , FrutasRESUMEN
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.
Asunto(s)
Anticarcinógenos , Neoplasias del Colon , Metformina , Humanos , Metformina/farmacología , Liposomas , Resultado del Tratamiento , Neoplasias del Colon/tratamiento farmacológicoRESUMEN
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.
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Anticarcinógenos , Apoptosis , Proliferación Celular , Glioma , Isotiocianatos , Fosfoglicerato Quinasa , Sulfóxidos , Humanos , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/patología , Glioma/metabolismo , Glioma/tratamiento farmacológico , Glioma/genética , Isotiocianatos/farmacología , Fosfoglicerato Quinasa/genética , Fosfoglicerato Quinasa/metabolismo , Transducción de Señal/efectos de los fármacos , Anticarcinógenos/farmacologíaRESUMEN
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.
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Compuestos Alílicos , Anticarcinógenos , Neoplasias de la Mama , Ajo , Lesiones Precancerosas , Humanos , Femenino , Ajo/metabolismo , Antioxidantes/farmacología , Benzo(a)pireno/toxicidad , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Apoptosis , Sulfuros/farmacología , Células Epiteliales/metabolismo , Anticarcinógenos/farmacología , Reparación del ADN , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/prevención & control , ADNRESUMEN
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.
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Anticarcinógenos , Ácidos Grasos , Animales , Bovinos , Humanos , Ácidos Grasos/química , Anticarcinógenos/farmacología , Caseínas/farmacología , Espectrometría de Masas en Tándem , Apoptosis , Células MCF-7RESUMEN
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.
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Anticarcinógenos , Antineoplásicos , Brassica , Isotiocianatos/farmacología , Verduras , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
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.
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Anticarcinógenos , Neoplasias Colorrectales , Estilbenos , Humanos , Resveratrol/farmacología , Resveratrol/uso terapéutico , Transducción de Señal , Factores de Transcripción , Anticarcinógenos/farmacología , Neoplasias Colorrectales/patología , Estilbenos/farmacología , Estilbenos/uso terapéuticoRESUMEN
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.