Back to Journals » Drug Design, Development and Therapy » Volume 13

Polyphyllin VI induces apoptosis and autophagy in human osteosarcoma cells by modulation of ROS/JNK activation

Authors Yuan YL, Jiang N, Li ZY, Song ZZ, Yang ZH, Xue WH, Zhang XJ, Du Y

Received 19 November 2018

Accepted for publication 25 July 2019

Published 28 August 2019 Volume 2019:13 Pages 3091—3103

DOI https://doi.org/10.2147/DDDT.S194961

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Sukesh Voruganti


Yong-Liang Yuan,1,* Neng Jiang,2,* Ze-Yun Li,1 Zhi-Zhen Song,1 Zhi-Heng Yang,1 Wen-Hua Xue,1 Xiao-Jian Zhang,1 Yue Du1

1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Pharmacy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China

Correspondence: Yong-Liang Yuan; Yue Du
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road 1, Zhengzhou, Henan 450052, People’s Republic of China
Tel/fax +86 03 716 629 5651
Email yylcpu@126.com; fccduy@zzu.edu.cn

*These authors contributed equally to this work

Purpose: Polyphyllin VI, a main active saponin isolated from traditional medicinal plant Paris polyphylla, has exhibited antitumor activities in several cancer cell lines. In the present study, we investigated the antitumor effect of Polyphyllin VI against human osteosarcoma cells (U2OS) and the underlying molecular mechanisms.
Methods: The U2OS cell lines were used to determine the antiproliferative effect of Polyphyllin VI by CCK8 assay. Cell cycle was analyzed by flow cytometry. The Polyphyllin VI-induced apoptosis was determined by Annexin V-APC/7-AAD apoptosis detection kit and JC-1 staining. Meanwhile, the autophagy was determined by acridine orange staining. The apoptosis and autophagy-related proteins were monitored by Western blot assay. Subsequently, intracellular hydrogen peroxide (H2O2) and the activation of ROS/JNK pathway were detected.
Results: Polyphyllin VI could potently inhibit cell proliferation by causing G2/M phase arrest. Polyphyllin VI induced mitochondria-mediated apoptosis with the upregulation of proapoptotic proteins Bax and poly ADP-ribose polymerase, and downregulation of antiapoptotic protein Bcl-2 in U2OS cells. Concomitantly, Polyphyllin VI provoked autophagy with the upregulation of critical Atg proteins and accumulation of LC3B-II. Intracellular H2O2 production was triggered upon exposure to Polyphyllin VI, which could be blocked by ROS scavenger. Polyphyllin VI dramatically promoted JNK phosphorylation, whereas it decreased the levels of phospho-p38 and ERK.
Conclusion: Our results reveal that Polyphyllin VI may effectively induce apoptosis and autophagy to suppress cell growth via ROS/JNK activation in U2OS cells, suggesting that Polyphyllin VI is a potential drug candidate for the treatment of osteosarcomas.

Keywords: Polyphyllin VI, osteosarcoma, apoptosis, autophagy, JNK activation

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]