Curcuminoid B63 Induces ROS-mediated Paraptosis-like Cell Death by Targeting TrxR1 in Gastric Cells

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2018 Dec 28

PMID 30590310

Citations 37

Authors

Xi Chen

Xiaoming Chen

Xi Zhang

Li Wang

Peihai Cao

Vinothkumar Rajamanickam

Chao Wu

Huiping Zhou

Yuepiao Cai

Guang Liang

Yi Wang

Affiliations

Soon will be listed here.

Abstract

Gastric cancer is one of the leading causes of cancer-related deaths. Chemotherapy has improved long-term survival of patients with gastric cancer. Unfortunately, cancer readily develops resistance to apoptosis-inducing agents. New mechanisms, inducing caspase-independent paraptosis-like cell death in cancer cells is presently emerging as a potential direction. We previously developed a curcumin analog B63 as an anti-cancer agent in pre-clinical evaluation. In the present study, we evaluated the effect and mechanism of B63 on gastric cancer cells. Our studies show that B63 targets TrxR1 protein and increases cellular reactive oxygen species (ROS) level, which results in halting gastric cancer cells and inducing caspase-independent paraptotic modes of death. The paraptosis induced by B63 was mediated by ROS-mediated ER stress and MAPK activation. Either overexpression of TrxR1 or suppression of ROS normalized B63-induced paraptosis in gastric cancer cells. Furthermore, B63 caused paraptosis in 5-fluorouracil-resistant gastric cancer cells, and B63 treatment reduced the growth of gastric cancer xenografts, which was associated with increased ROS and paraptosis. Collectively, our findings provide a novel strategy for the treatment of gastric cancer by utilizing TrxR1-mediated oxidative stress generation and subsequent cell paraptosis.

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