Cepharanthine combined with 5-fluorouracil inhibits the growth of p53-mutant human colorectal cancer cells

Abstract

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.

Graphical abstract

Keywords:

• 5-FU
• ABC transporter
• apoptosis
• BAK
• cepharanthine
• colorectal cancer

Acknowledgments

We thank Mr. Noppadol Saardlam at the Immunology Laboratory, Faculty of Dentistry, Chulalongkorn University for flow cytometric analysis.

Disclosure of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksompot Endowment Fund), grant number GCUGR1125582038M (SU), Rathchadaphiseksomphot Fund, Chulalongkorn University, grant number RA57/089 (PW), and Special Task Force for Activating Research (STAR) Ratchadaphiseksomphot Endowment Fund, Chulalongkorn University, grant number GSTAR 59-005-30-001.