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E platinum, a newly synthesized platinum compound, induces apoptosis through ROS‐triggered ER stress in gastric carcinoma cells
Author(s) -
Wang Xiaoping,
Guo Qinglong,
Tao Lei,
Zhao Li,
Chen Yan,
An Teng,
Chen Zhen,
Fu Rong
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22486
Subject(s) - unfolded protein response , apoptosis , endoplasmic reticulum , biology , cancer cell , cisplatin , programmed cell death , cancer research , reactive oxygen species , cancer , microbiology and biotechnology , biochemistry , chemotherapy , genetics
Gastric cancer (GC) is still one of the leading causes of death in cancer‐related diseases. In this study, we aimed to investigate the antitumor effect of E Platinum, a newly platinum‐based chemotherapeutic agent bearing the basic structure of Oxaliplatin, in a variety of gastric carcinoma cells and the underlying mechanisms. We demonstrated that E Platinum significantly induced apoptosis in gastric cancer cells via mitochondrial apoptotic pathway as a result of increased reactive oxygen species (ROS). We also found that E Platinum enhanced Ca 2+ flux out from the endoplasmic reticulum by increasing the protein expression of IP3R type 1 (IP3R1) and decreasing the expression of ERp44. Dysfunction of Ca 2+ homeostasis in endoplasmic reticulum (ER) leads to accumulation of unfolded proteins and ER stress. Mechanically, E Platinum increased ER stress associated protein expression such as GRP78, p‐PERK, p‐eIF2α, ATF4, and CHOP. However, knocking down CHOP reversed E Platinum‐induced apoptosis by blocking mitochondrial apoptotic pathway. Furthermore, 10 mg/kg of E Platinum significantly suppressed BGC‐823 tumor growth in vivo without toxicity, which correlated with induction of apoptosis and expression of ER stress related proteins in tumor tissues. Taken together, E Platinum inhibited tumor growth and induced apoptosis by ROS‐mediated ER stress activation both in vitro and in vivo. Our study indicated that E Platinum may be a potential and effective treatment for gastric cancer in clinical. © 2016 Wiley Periodicals, Inc