The synergistic anticancer effect of formosanin C and polyphyllin VII based on caspase-mediated cleavage of Beclin1 inhibiting autophagy and promoting apoptosis

Abstract

Objectives: Drug combination has a promising and potential development prospect in the treatment of various cancers. The objective of this study is to investigate the synergistic mechanisms of polyphyllin VII (PVII) and formosanin C (FC) in lung cancer. Materials and methods: The combination of FC and PVII influenced on the apoptosis, autophagy, and the relative signalling pathways were analysed in lung cancer cells. Results: The combination of FC and PVII demonstrated a concentration- dependent growth inhibition in human lung cancer cells. The combination index (CI) obtained from four lung cancer cells was smaller than 1. This synergistic antitumour effect was based on the increase of their single proapoptotic effect but inhibiting FC-induced autophagy in NCI-H460 cells. FC and PVII activated proapoptotic elements like cleaved-caspase-3, -8, and -9 to induce Beclin1 cleaved into Beclin1-C which suppressed FC-triggered autophagy and enhanced apoptosis. Conclusions: Formosanin C and PVII showed a synergistic antitumour effect on lung cancer cells. The findings would provide the foundation for the use of combination drugs in the future.