RESUMO
BACKGROUND: Telomerase has been considered as an attractive molecular target for breast cancer therapy. The main objective of this work is to assess the inhibitory effects of silibinin and curcumin, two herbal substances, on telomerase gene expression in breast cancer cells. MATERIALS AND METHODS: For determination of cell viability tetrazolium-based assays were conducted after 24, 48, and 72 h exposure times and expression of human telomerase reverse transcriptase gene was measured with real-time PCR. RESULTS: Each compound exerted cytotoxic effects on T47D cells and inhibited telomerase gene expression, both in a time-and dose-dependent manner. The mixture of curcumin and silibinin showed relatively more inhibitory effect on growth of T47D cells and hTERT gene expression as compared with either agent alone. CONCLUSIONS: These findings suggest that cell viability along with hTERT gene expression in breast cancer cells could be reduced by curcumin and silibinin.
Assuntos
Neoplasias da Mama/enzimologia , Curcumina/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Silimarina/farmacologia , Telomerase/antagonistas & inibidores , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Silibina , Telomerase/genética , Telomerase/metabolismo , Células Tumorais CultivadasRESUMO
Leptin plays the role of mitogenic factor in the breast carcinogenesis. Therefore, it could be considered as a target for breast cancer therapy. Leptin gene expression could be modulated by activation of estrogen receptors. Silibinin is an herbal compound with anti-cancer activity on prostate and colorectal cancers. Based on the fact that targeting of leptin can be considered as a novel strategy for breast cancer therapy, the aim of this study was the investigation of potentiality of silibinin for inhibition of leptin gene expression and secretion, and its link with expression of estrogen receptors. Cytotoxic effect of silibinin on T47D breast cancer cells was investigated by MTT assay test after 24, 48 and 72 h treatments with different concentrations of silibinin. The levels of leptin, estrogen receptor α and estrogen receptor ß genes expression was measured by reverse-transcription real-time PCR. The amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. Silibinin inhibits growth of T47D cells in a time and dose dependent manner. There was significant difference between control and treated cells in the levels of leptin, estrogen receptor ß expression levels and the quantity of secreted leptin was decreased in the treated cells in comparison to control cells. In conclusion, silibinin inhibits the expression and the secretion of leptin and in the future it might probably be a drug candidate for breast cancer therapy through leptin targeting.
