RESUMO
Eleven derivatives from Antrodia camphorata were isolated in order to evaluate their selective cytotoxicity toward 14 types of human cancer cell and two non-transformed cell types. Among these triterpenoids, methyl antcinate A (MAA) exhibited the most potent spectrum of anticancer effects in KB cells, four different oral cancer cell lines (TSCCa, GNM, OC-2, and OEC-M1), Panc-1, BT474, PC-3, OVCAR-3, HeLa, and U2OS cells with high selectivity indices (CC(50)/IC(50)). The expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and poly(ADP-ribose) polymerase (PARP) of PC-3 cells tested by western blotting suggested that MAA exerts cell death through the caspase-dependent cascade and the Bax-mediated mitochondrial apoptotic pathway, not only on liver and oral cancer cells but on other types as well, including prostate cancer, in a dose-dependent manner. In addition to MAA, methyl antcinate B, dehydroeburicoic acid, and 15α-acetyl-dehydrosulfurenic acid also exhibited significant selective cytotoxic effects to respective cancer cells. Modifications of these triterpenoids may lead to the development of more potent anticancer drugs.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antrodia/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Humanos , Células KB , Neoplasias Bucais/tratamento farmacológico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologiaRESUMO
AIM: The study of the anticancer effects of destruxin B (DB) is rare and its anticancer mechanism remains unknown. The aim of this study was to test the in vitro and in vivo anticancer effects of DB, on human HT-29 colorectal cancer (CRC). MATERIALS AND METHODS: DB was isolated and characterized by high pressure liquid chromatography, electrospray ionization mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the effects of DB on HT-29 cells in vitro. The anticancer effects of DB were investigated in a murine xenograft model of human colon cancer. RESULTS: A significant inhibition of cell viability was observed with DB treatment in time- and dose-dependent manners. DB administered subcutaneously daily at 0.6-15 mg/kg was proven to be safe and effective in inhibiting the growth of CRC cells. Expression of Bax, cleaved poly (ADP-ribose) polymerase and active caspase-3 were observed with DB treatment and the increase in tumor volumes of treated groups were significantly (p<0.05) lower than those of the mock-treated group. CONCLUSION: DB has potential as a new therapeutic agent against human CRC.