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G15, a GPR30 antagonist, induces apoptosis and autophagy in human oral squamous carcinoma cells. | LitMetric

G15, a GPR30 antagonist, induces apoptosis and autophagy in human oral squamous carcinoma cells.

Chem Biol Interact

College of Medicine, China Medical University, Taichung 40402, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan.

Published: November 2013

AI Article Synopsis

Article 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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Source
http://dx.doi.org/10.1016/j.cbi.2013.10.014DOI Listing

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