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Triptonide Modulates MAPK Signaling Pathways and Exerts Anticancer Effects via ER Stress-Mediated Apoptosis Induction in Human Osteosarcoma Cells

Authors Zheng L, Fang S, Hui J, Rajamanickam V, Chen M, Weng Q, Wu X, Zhao Z, Ji J

Received 20 April 2020

Accepted for publication 10 June 2020

Published 17 July 2020 Volume 2020:12 Pages 5919—5929

DOI https://doi.org/10.2147/CMAR.S258203

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Liyun Zheng,1,2,* Shiji Fang,1,2,* Junguo Hui,3 Vinothkumar Rajamanickam,2 Minjiang Chen,2 Qiaoyou Weng,2 Xulu Wu,2 Zhongwei Zhao,1 Jiansong Ji1– 3

1Interventional Diagnosis and Treatment Center, Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, People’s Republic of China; 2Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, People’s Republic of China; 3Department of Radiology, Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiansong Ji
Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, People’s Republic of China
Tel +86-13648782878
Fax +86-578-2133457
Email lschrjjs@163.com

Background: Osteosarcoma (OS) is the most common primary malignancy arise from bone and is one of the causes of cancer-related deaths. Triptonide (TN), a diterpenoid epoxide presented in Tripterygium wilfordii, is shown to possess a broad spectrum of biological properties.
Methods: In this study, we investigate the growth inhibitory effect of TN against human OS cells and its underlying molecular mechanism of action.
Results: Findings of our in vitro study revealed that TN exhibited a dose-dependent cytotoxic effect in MG63 and U-2OS cells. ROS-mediated cytotoxic effect was achieved in OS cells treated with TN which was reversed upon NAC treatment. Significantly, increased expression of PERK, p-EIF2, GRP78, ATF4 and CHOP in TN-treated OS cells unfolds the molecular mechanism of TN targets ER stress-mediated apoptosis. Modulation of ERK MAPK pathway was also observed as evidenced by the increased phosphorylation of ERK (p-ERK) and p-p38 in TN-treated OS cells.
Conclusion: Altogether, the outcome of the study for the first time revealed that TN exhibited its potential chemotherapeutic effects through ROS-mediated ER stress-induced apoptosis via p38 and ERK MAPK signaling pathways.

Keywords: osteosarcoma, triptonide, ER stress, apoptosis, MAPK signaling

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