期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 264, 期 -, 页码 1-9出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2017.01.004
关键词
Paris saponin; Apoptosis; Autophagy
资金
- National Natural Science Foundation of China [81302654, 81673670]
- Science and Technology Program of Guangzhou [201610010108, 201300000041]
- Fundamental Research Funds for the Central Universities [21615413]
- Jinan Double Hundred Talents Plan
Paris saponins possess anticancer, anti-inflammatory, and antiviral effects. However, the anticancer effect of Paris saponins has not been well elucidated and the mechanisms underlying the potential function of Paris saponins in cancer therapy are needed to be further identify. In this study, we report that saponin compounds isolated from Paris polyphylla exhibited antitumor activity against breast cancer cell lines, MCF-7 and MDA-MB-231. Paris saponin XA-2 induced apoptosis in both cell lines, as evidenced by the activation of caspases and cleavage of Poly (ADP-ribose) polymerase. The ability of XA-2 to induce autophagy was confirmed by acridine orange staining, accumulation of autophagosome-bound Long chain 3 (LC3)-II, and measurement of autophagic flux. XA-2-induced autophagy was observed to promote apoptosis by the combined treatment of breast cancer cell lines with XA-2 and autophagy inhibitors 3-methyladenine and bafilomycin Al, respectively. Moreover, we report a decrease in the levels of Akt/ mTOR signaling pathway proteins, such as the phosphorylated forms of Akt, mTOR, P70S6K, and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). Taken together, these results provide important insights explaining the anticancer activity of Paris saponins and the potential development of XA-2 as a new therapeutic agent.(C) 2017 Elsevier B.V. All rights reserved.
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