RESUMEN
Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.
Asunto(s)
Antineoplásicos/farmacología , Carcinógenos/toxicidad , Glucosinolatos/farmacología , Neoplasias Hepáticas/patología , Hígado/efectos de los fármacos , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Masculino , Proteínas Proto-Oncogénicas c-mdm2/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Chlorogenic acid (1), salvianolic acid B (2), and tanshinone IIA (3) are commonly used as chemoprotective agents for chemotherapy in cancer patients. The present study deals with the effect of these three compounds on cytotoxicity of doxorubicin in HepG2 cells. The results showed that 1 and 2 reduced the cytotoxicity of doxorubicin through scavenging ROS generated by doxorubicin in HepG2 cells. The findings suggest that 1 and 2 could enhance the expression of SOD and decrease that of NADPH oxidase, which resulted in the elimination of ROS. On the contrary, 3 enhanced the cytotoxicity of doxorubicin in HepG2 cells. Furthermore, drug interactions between doxorubicin and 3 produce synergistic effects in HepG2 cells.