Polyphyllin D induces apoptosis and protective autophagy in breast cancer cells through JNK1-Bcl-2 pathway.

Abstract Ethnopharmacological relevance Polyphyllin D (PD), an active component from rhizome of Paris polyphylla Sm, root and rhizome, shows a strong anti-cancer activity in several cancers. However, whether autophagy is involved in PD-induced cell death in breast cancer cells and its molecular mechanism has not yet been elucidated. Aim of the study To explore the anti-tumor effects of PD in breast cancer and the underlying mechanisms. Materials and methods PD was isolated from P. polyphylla Sm and confirmed by HPLC and NMR. The role of PD in cell viability, apoptosis, autophagy in breast cancer cells were determined. Results PD shows significant anti-tumor activity by inhibit cell proliferation and induce caspase-dependent apoptosis in breast cancer cells. Moreover, PD treatment could induce autophagy by activation of JNK1/Bcl-2 pathway. Importantly, blocking of autophagy by using autophagy inhibitor 3-methyladenine (3-MA) dramatically increase PD-induced apoptosis as evidence by the increased percentage of apoptotic cell death. The anti-tumor effects of PD also investigated in vivo. The results showed that the combinatory treatment of PD with autophagy inhibitor significantly promote PD-induced apoptosis. Conclusion PD could induce caspase-dependent apoptosis and cyto-protectvie autophagy by activation of JNK1/Bcl-2 pathway in breast cancer cells. Combination with an autophagy inhibitor significantly enhance cytotoxic effect of PD and this combination may be a promising candidate for breast cancer therapy.