G15, a GPR30 antagonist,induces apoptosis and autophagy in human oral squamous carcinoma cells |
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Authors: | Li-Yuan Bai Jing-Ru Weng Jing-Lan Hu Dasheng Wang Aaron M. Sargeant Chang-Fang Chiu |
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Affiliation: | 1. College of Medicine, China Medical University, Taichung 40402, Taiwan;2. Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan;3. Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan;4. Cancer Center, China Medical University Hospital, Taichung 40447, Taiwan;5. Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA;6. Charles River Laboratories, Preclinical Services, Spencerville, OH 45887, USA |
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Abstract: | As GPR30 has been implicated in mediating cancer cell proliferation, this study aimed to examine the antitumor effect of the GPR30 antagonist G15 in human oral squamous cell carcinoma (OSCC). G15 induced dose-dependent cytotoxicity, apoptosis and G2/M cell cycle arrest in a panel of OSCC cells. The results showed that G15 could inhibit the growth of the oral cancer cells with IC50 value 11.2 μM for SCC4, 15.6 μM for SCC9, and 7.8 μM for HSC-3, respectively. Flow cytometric analysis and Comet assay indicated that G15 suppressed the viability of SCC4 and HSC-3 cells by inducing apoptosis and G2/M arrest. In addition, G15 down regulated the expression of Akt, cell cycle-related proteins, and mitogen-activated protein kinases, but increased the levels of LC3B-II and the accumulation of autophagosomes. Inhibition of autophagy by chloroquine does not affect the G15-induced apoptosis in SCC4 cells. Mechanistic evidence indicated that the antiproliferative effect was mediated through the downregulation of cdc2, cdc25c and NF-κB expression. Taken together, our findings suggest the potential of G15 in treating OSCC. |
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Keywords: | GPR30 G15 Oral cancer Autophagy Apoptosis |
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