GABAA receptor-binding protein promotes sensitivity to apoptosis induced by chemotherapeutic agents

Rho,Seung  Bae; Byun,Hyun-Jung; Kim,Boh-Ram; Kim,Ik  Sun; Lee,Jeong  Heon; Yoo,Richard; Park,Sung  Taek; Park,Sung   Ho

doi:10.3892/ijo.2013.1866

GABAA receptor-binding protein promotes sensitivity to apoptosis induced by chemotherapeutic agents

Authors:
- Seung Bae Rho
- Hyun-Jung Byun
- Boh-Ram Kim
- Ik Sun Kim
- Jeong Heon Lee
- Richard Yoo
- Sung Taek Park
- Sung Ho Park
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Affiliations: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea, Department of Obstetrics and Gynecology, Chonbuk National University Medical School, Jeonju 561‑712, Republic of Korea, Department of Biochemistry, University of Washington, Seattle, WA 98195, USA, Department of Obstetrics and Gynecology, Hallym University, Seoul 150-950, Republic of Korea
Published online on: March 27, 2013 https://doi.org/10.3892/ijo.2013.1866
Pages: 1807-1814

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Abstract

In the present study, the expression of human γ-aminobutyrate type A (GABAA) receptor-binding protein (GABARBP) is downregulated in ovarian cancer cell lines and tissues. We also found that the specific function of GABAPBP was that of a novel pro-apoptotic protein. Both GABARBP and cisplatin suppressed cancer cell proliferation in a concentration-dependent manner. The combined treatment of GABARBP and cisplatin was more effective in inhibiting cell growth, as well as cell migration, than with either drug treatment alone. At the same time, the treatment combination is correlated with the downregulation of cyclin D1 and CDK4, arrested cell cycle progression in the G0-G1 phase and enhancing p53 expression, while also reducing Bcl-2 and Bcl-xL expression. The p53 and p21 promoter luciferase activities were induced by GABARBP, whereas there was no effect on the p53-/- and p21-/- system. In addition, p53 activity was validated with UV irradiation and siGABARBP. Taken together, our results indicate that GABARBP can regulate the pro-apoptotic activity of cisplatin via the upregulation of p53 expression.

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