Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants

0464321 - BÚ 2017 RIV US eng J - Journal Article
Babica, Pavel - Čtveráčková, Lucie - Lenčešová, Zuzana - Trosko, J. E. - Upham, B. L.
Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants.
Nutrition and Cancer-An International Journal. Roč. 68, č. 5 (2016), s. 827-837. ISSN 0163-5581. E-ISSN 1532-7914
R&D Projects: GA MŠMT LH12034
Institutional support: RVO:67985939
Keywords : gap junctional intercellular communication * chemopreventive agents * environmental toxicants
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 2.447, year: 2016

Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30min or 24h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity.
Permanent Link: http://hdl.handle.net/11104/0265328