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KMID : 0624620190520110647
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BMB Reports
2019 Volume.52 No. 11 p.647 ~ p.652
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G protein-coupled estrogen receptor-1 agonist induces chemotherapeutic effect via ER stress signaling in gastric cancer
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Lee Seon-Jin
Kim Tae-Woo
Park Gyeong-Lim
Hwang Yo-Sep
Cho Hee-Jun
Kim Jong-Tae
Lee Hee-Gu
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Abstract
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G protein-coupled estrogen receptor (GPER) is known to play an important role in hormone-associated cancers. G-1, a novel synthetic GPER agonist, has been reported to exhibit anti-carcinogenic properties. However, the chemotherapeutic mechanism of GPER is yet unclear. Here, we evaluated GPER expression in human gastric cancer tissues and cells. We found that G-1 treatment attenuates GPER expression in gastric cancer. GPER expression increased G-1-induced antitumor effects in mouse xenograft model. We analyzed the effects of knockdown/overexpression of GPER on G-1-induced cell death in cancer cells. Increased GPER expression in human gastric cancer cells increased G-1-induced cell death via increased levels of cleaved caspase-3, -9, and cleaved poly ADP-ribose polymerase. Interestingly, during G-1-induced cell death, GPER mRNA and protein expression was attenuated and associated with ER stress-induced expression of PERK, ATF-4, GRP-78, and CHOP. Furthermore, PERK-dependent induction of ER stress activation increased G-1-induced cell death, whereas PERK silencing decreased cell death and increased drug sensitivity. Taken together, the data suggest that the induction of ER stress via GPER expression may increase G-1-induced cell death in gastric cancer cells. These results may contribute to a new paradigm shift in gastric cancer therapy.
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KEYWORD
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Cell death, ER stress, G-1, Gastric cancer, GPER
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