title: Paris saponin-induced autophagy promotes breast cancer cell apoptosis via the Akt/mTOR signaling pathway.
abstract: 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 A1, 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.
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Zhan-Zhi
authors.initials: ZZ
authors.lastname: Xie
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Man-Mei
authors.initials: MM
authors.lastname: Li
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Deng
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Lu
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Liu-Bing
authors.initials: LB
authors.lastname: Hu
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Zui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Hui-Yang
authors.initials: HY
authors.lastname: Jie
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Guangdong Institute for Drug Control, Guangzhou 510632, China. Electronic address: cpulxx@126.com.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China. Electronic address: tliuzh@jnu.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019668:Liliaceae / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Apoptosis; Autophagy; Paris saponin