PEITC triggers multiple forms of cell death by GSH-iron-ROS regulation in K7M2 murine osteosarcoma cells.

Acta Pharmacologica Sinica
Huan-Huan LvPeng Shang

Abstract

Phenethyl isothiocyanate (PEITC) is an isothiocyanate that largely exists in cruciferous vegetables and exhibits chemopreventive and chemotherapeutic potential against various cancers. However, it is little known about the molecular mechanisms of its antitumor action against osteosarcoma, which is the second highest cause of cancer-related death in children and adolescents. In this study, we investigated the effects of PEITC on K7M2 murine osteosarcoma both in vitro and in vivo. We found that treatment with PEITC dose-dependently inhibited the viability of K7M2 murine osteosarcoma cells with an IC50 value of 33.49 μM at 24 h. PEITC (1, 15, 30 μM) dose-dependently inhibited the cell proliferation, caused G2/M cell cycle arrest, depleted glutathione (GSH), generated reactive oxygen species (ROS), altered iron metabolism, and triggered multiple forms of cell death, namely ferroptosis, apoptosis, and autophagy in K7M2 cells. We further revealed that PEITC treatment activated MAPK signaling pathway, and ROS generation was a major cause of PEITC-induced cell death. In a syngeneic orthotopic osteosarcoma mouse model, administration of PEITC (30, 60 mg/kg every day, ig, for 24 days) significantly inhibited the tumor growth, but higher ...Continue Reading

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Citations

Oct 14, 2020·Biochemistry. Biokhimii︠a︡·E V Kalinina, L A Gavriliuk
Jan 5, 2021·Biotechnology and Applied Biochemistry·Zhengxin WuXuehui Hong
Dec 10, 2020·Biomarker Research·Zhaoqing LiJichun Zhou
Mar 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Kai ZhengZhendan He
Apr 20, 2021·Frontiers in Oncology·Zhiyuan ShiChen Shao
May 12, 2021·ACS Nano·Xiaotong ChengFu-Gen Wu
Aug 5, 2021·Journal of Bone Oncology·Jiazheng ZhaoHelin Feng

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Methods Mentioned

BETA
protein assay
flow cytometry
MDA

Software Mentioned

GraphPad Prism

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