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Front. Pharmacol. | doi: 10.3389/fphar.2018.00814

Gambogic acid and its analogs inhibit gap junctional intercellular communication

 Eun Ju Choi1, Joo Hye Yeo1, Sei Mee Yoon1, 2 and  Jinu Lee1*
  • 1College of Pharmacy, Yonsei University, South Korea
  • 2Department of Integrated OMICS for Biomedical Sciences, Yonsei University, South Korea

Gap junctions are intercellular channels composed of connexins. Cellular molecules smaller than 1 kDa can diffuse through gap junctions by a process termed gap junctional intercellular communication (GJIC), which plays essential roles in various pathological and physiological conditions. Gambogic acid, a major component of a natural yellow dye, has been used as traditional medicine and has been reported to have various therapeutic effects, including an anti-cancer effect. In this study, two different gap junction assay methods showed that gambogic acid and its analogs inhibited GJIC. The inhibition was rapidly reversible and was not mediated by changes in surface expression or S368 phosphorylation of Cx43, cellular calcium concentration, or redox state. We also developed an assay system to measure the intercellular communication induced by Cx40, Cx30, and Cx43. Dihydrogambogic acid potently inhibited GJIC by Cx40 (IC50 = 5.1 μM), whereas the IC50 value of carbenoxolone, which is known as a broad spectrum GJIC inhibitor, was 105.2 μM. Thus, dihydrogambogic acid can act as a pharmacological tool for the inhibition of Cx40.

Keywords: Gambogic acid, dihydrogambogic acid, tetrahydrogambogic acid, gap junction, connexin, cx40

Received: 04 Apr 2018; Accepted: 09 Jul 2018.

Edited by:

Eleonora Grandi, University of California, Davis, United States

Reviewed by:

Francis A. Ortega, Physiology, Biophysics, and Systems Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, United States
Hai M. Nguyen, University of California, Davis, United States  

Copyright: © 2018 Choi, Yeo, Yoon and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jinu Lee, College of Pharmacy, Yonsei University, Incheon, South Korea, jinulee@yonsei.ac.kr