Polyphyllin D induces apoptosis and protective autophagy in breast cancer cells through JNK1-Bcl-2 pathway. (10th January 2022)

• Record Type: Journal Article
• Authors: Liu, Jiazhe; Liu, Yongzhi; Li, Hongchang; Wei, Chuangchao; Mao, Anwei; Liu, Weiyan; Pan, Gaofeng
• Is Part Of: Journal of ethnopharmacology. Volume 282(2021)
• Publication Date: 2022-01-10
• Subjects: Autophagy -- Apoptosis -- Breast cancer -- JNK -- Bcl-2; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.114591
• Languages: English
• ISSNs: 0378-8741

Abstract

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. Graphical abstract: Image 1