Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells

Gap junctions are molecular structures that allow communication between neighboring cells. It has been shown that gap junctional intercellular communication (GJIC) is notoriously reduced in cancer cells compared to their normal counterparts. Ouabain, a plant derived substance, widely known for its t...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-12, Vol.22 (1), p.358
Main Authors: Serrano-Rubi, Mauricio, Jimenez, Lidia, Martinez-Rendon, Jacqueline, Cereijido, Marcelino, Ponce, Arturo
Format: Article
Language:English
Subjects:
Apoptosis
cancer
Cardiotonic Agents - pharmacology
Cell Communication
Cell Proliferation
gap junctions
Gap Junctions - drug effects
Humans
Neoplasms - drug therapy
Neoplasms - metabolism
Neoplasms - pathology
ouabain
Ouabain - pharmacology
Signal Transduction
Tumor Cells, Cultured
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Summary:Gap junctions are molecular structures that allow communication between neighboring cells. It has been shown that gap junctional intercellular communication (GJIC) is notoriously reduced in cancer cells compared to their normal counterparts. Ouabain, a plant derived substance, widely known for its therapeutic properties on the heart, has been shown to play a role in several types of cancer, although its mechanism of action is not yet fully understood. Since we have previously shown that ouabain enhances GJIC in epithelial cells (MDCK), here we probed whether ouabain affects GJIC in a variety of cancer cell lines, including cervico-uterine (CasKi, SiHa and Hela), breast (MDA-MB-321 and MCF7), lung (A549), colon (SW480) and pancreas (HPAF-II). For this purpose, we conducted dye transfer assays to measure and compare GJIC in monolayers of cells with and without treatment with ouabain (0.1, 1, 10, 50 and 500 nM). We found that ouabain induces a statistically significant enhancement of GJIC in all of these cancer cell lines, albeit with distinct sensitivity. Additionally, we show that synthesis of new nucleotides or protein subunits is not required, and that Csrc, ErK1/2 and ROCK-Rho mediate the signaling mechanisms. These results may contribute to explaining how ouabain influences cancer.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22010358