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

Liyun Zheng; Shiji Fang; Junguo Hui; Vinothkumar Rajamanickam; Minjiang Chen; Qiaoyou Weng; Xulu Wu; Zhongwei Zhao; Jiansong Ji

doi:10.2147/CMAR.S258203

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

Cancer Manag Res. 2020 Jul 17:12:5919-5929. doi: 10.2147/CMAR.S258203. eCollection 2020.

Authors

Liyun Zheng^#^{1

2}, Shiji Fang^#^{1

2}, Junguo Hui³, Vinothkumar Rajamanickam², Minjiang Chen², Qiaoyou Weng², Xulu Wu², Zhongwei Zhao¹, Jiansong Ji^{1

2

3}

Affiliations

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

^# Contributed equally.

Abstract

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: ER stress; MAPK signaling; apoptosis; osteosarcoma; triptonide.