Allylated Curcumin Analog CA6 Inhibits TrxR1 and Leads to ROS-Dependent Apoptotic Cell Death in Gastric Cancer Through Akt-FoxO3a

作者：V Rajamanickam, Tao Yan, WU Li-min, Zhao Y, Xinhua Xu, Zhu H, Xiaofeng Chen, M Wang, Liu Z, Liu Z, Liang G, Y Wang · 发表于：DOAJ (DOAJ: Directory of Open Access Journals) · 年份：2020 · 研究领域：Tannin, Tannase and Anticancer Activities、Genomics, phytochemicals, and oxidative stress、Curcumin's Biomedical Applications

Vinothkumar Rajamanickam,* Tao Yan,* Liangrong Wu, Yanni Zhao, Xiaohong Xu, Heping Zhu, Xi Chen, Meihong Wang, Zhoudi Liu, Zhiguo Liu, Guang Liang, Yi Wang Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi WangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of ChinaTel/Fax +86- 577-85773060Email yi.wang1122@wmu.edu.cnBackground: Gastric cancer is one of the leading causes of cancer-related deaths. Allylated monocarbonyl analogs of curcumin (MACs) have been reported to selectively inhibit a broad range of human cancers including gastric cancer. However, the precise molecular mechanisms underlying the inhibitory activities of MACs are not fully known.Methods: In this study, we examined the anti-tumor activities of an allylated MAC, CA6, on gastric cancer cells and gastric cancer xenograft mouse model. The potential molecular anti-tumor mechanisms of CA6 were also elucidated.Results: Our data show that CA6 exhibited significant cytotoxicity in gastric cancer cells, which was seen as an induction of G2/M cell cycle arrest and apoptosis. These activities were mediated through an elaboration of ROS levels in gastric cancer cells and induction of endoplasmic reticulum stress. CA6 increased ROS levels t...