6-Shogaol mediated ROS production and apoptosis via endoplasmic reticulum and mitochondrial pathways in human endometrial carcinoma Ishikawa cells
Run‐Hui Ma, Zhi‐Jing Ni, Fan Zhang, Yuanyuan Zhang, Miaomiao Liu, Kiran Thakur, Jian‐Guo Zhang, Shaoyun Wang, Zhao‐Jun Wei
Abstract
Endometrial cancer (EC) associated with endogenous hormone metabolism, obesity, diabetes, and inappropriate dietary habits has shown a rising trend in recent years. Various therapeutics methods including dietary approaches (vital phytochemicals) offer healthy and nontoxic strategies against cancer. To date, 6-shogaol as one of the antitumor phytochemicals remains unexplored against human endometrial cancer cells. In our study, 6-shogaol obtained from Zingiber officinale rhizomes separated and purified by HPLC, LC-MS/MS, and NMR respectively could inhibit Ishikawa cell proliferation at IC50 (24.91 μM) with the arrested cell cycle in the G2/M phase. Moreover, it promoted apoptosis, as a result, triggered ROS production, then activated key ER response biomarkers in Ishikawa cell associated with mitochondria, and ultimately regulated related genes and proteins in vitro and in vivo. Therefore, 6-shogaol can be used as a promising natural compound endowed with potential benefits for cancer treatment and/or prevention at large and EC in particular.