ANTICANCER EFFECTS OF CEPHARANTHINE ON HUMAN COLORECTAL CANCER CELLS

Abstract

Cepharanthine (CEP), a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata, exhibits anticancer activity against several different types of cancer including oropharynx cancer, leukemia, hepatocarcinoma and cholangiocarcinoma. This study aimed to investigate the cytotoxic effect of CEP and its underlying molecular mechanisms of action in human colorectal cancer cells. Two colorectal cancer cell lines, COLO 205 (COX-2 negative and p53 wild-type) and HT-29 (COX-2 positive and p53 mutant) were used. In the present study, CEP was found to exhibit cytotoxicity in COLO 205 and HT-29 cells in a concentration-dependent manner. Notably, CEP was more toxic to HT-29 cells (IC50 = 6.12±1.68 µM) than COLO 205 cells (IC50 = 32.13±0.515 µM). Additionally, CEP could significantly trigger both colorectal cancer cell lines to undergo apoptosis and cell cycle arrest at G1/S phase. Mechanistic studies illustrated that CEP could down-regulate the expression of anti-apoptotic, Bcl-2 and Mcl-1 genes in COLO 205 cells and Bcl-xl gene in HT-29 cells. CEP also significantly increased reactive oxygen species (ROS) level in both COLO 205 and HT-29 cells and cytotoxic activity of CEP was abolished by N-acetylcysteine (NAC). Moreover, CEP was able to down-regulate the expression of COX-2 gene in HT-29 cells. Taken together, the results of this study suggest that the anticancer effects of CEP involve induction of apoptosis, cell cycle arrest and ROS generation as well as inhibition of COX-2 gene expression, illustrating a therapeutic potential of CEP in colorectal cancer treatment.