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

Liyun Zheng1,2, Shiji Fang1,2, Junguo Hui3

  • 1Interventional Diagnosis and Treatment Center, Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, People's Republic of China.

Cancer Management and Research
|August 9, 2020
PubMed
Abstract

Insights

Triptonide (TN) shows potential as a chemotherapy agent for osteosarcoma (OS). It induces cancer cell death by triggering reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress and apoptosis through MAPK signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma (OS) is a primary bone cancer and a significant cause of cancer mortality.
  • Triptonide (TN), derived from Tripterygium wilfordii, exhibits diverse biological activities.

Purpose of the Study:

  • To investigate the anti-cancer effects of Triptonide (TN) on human osteosarcoma (OS) cells.
  • To elucidate the molecular mechanisms underlying TN's cytotoxic action in OS.

Main Methods:

  • In vitro assessment of TN's cytotoxic effects on MG63 and U-2OS osteosarcoma cell lines.
  • Analysis of reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress markers (PERK, p-EIF2, GRP78, ATF4, CHOP).
  • Evaluation of mitogen-activated protein kinase (MAPK) pathway modulation, including ERK and p38 phosphorylation.

Main Results:

  • TN demonstrated a dose-dependent cytotoxic effect on OS cells.
  • TN-induced cytotoxicity was mediated by increased ROS production, which was reversed by N-acetylcysteine (NAC).
  • TN treatment upregulated ER stress markers and modulated ERK and p38 MAPK pathways, indicating apoptosis induction.

Conclusions:

  • Triptonide (TN) exhibits chemotherapeutic potential against osteosarcoma.
  • TN induces apoptosis in OS cells via ROS-mediated ER stress, involving the p38 and ERK MAPK signaling pathways.
Keywords:
ER stressMAPK signalingapoptosisosteosarcomatriptonide

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