Mutant p53 is primarily responsible for ineffectiveness of many anticancer drugs. The present study showed that cepharanthine alone or combined with 5-fluorouracil effectively controlled the growth of HT-29 human colorectal cancer cells harboring mutant p53 both in vitro and in vivo. The combination of cepharanthine and 5-fluorouracil additively induced apoptotic and necrotic cell death. Their combination significantly upregulated the expression of BAK and cleaved PARP in tumor tissues. Moreover, cepharanthine could prevent 5-fluorouracil-induced BCRP and MRP1 expression. These findings suggest that cepharanthine is a promising agent for treating patients with colorectal cancer containing p53 mutation.
Keywords: 5-FU; ABC transporter; BAK; apoptosis; cepharanthine; colorectal cancer.