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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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/358 |
| _version_ | 1797542848749371392 |
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| author | Mauricio Serrano-Rubi Lidia Jimenez Jacqueline Martinez-Rendon Marcelino Cereijido Arturo Ponce |
| author_facet | Mauricio Serrano-Rubi Lidia Jimenez Jacqueline Martinez-Rendon Marcelino Cereijido Arturo Ponce |
| author_sort | Mauricio Serrano-Rubi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T13:36:18Z |
| format | Article |
| id | doaj.art-e36ba374123446fe945870dcb69d5e6a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:36:18Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e36ba374123446fe945870dcb69d5e6a2023-11-21T07:30:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122135810.3390/ijms22010358Ouabain Promotes Gap Junctional Intercellular Communication in Cancer CellsMauricio Serrano-Rubi0Lidia Jimenez1Jacqueline Martinez-Rendon2Marcelino Cereijido3Arturo Ponce4Department of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico City C.P. 07360, MexicoDepartment of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico City C.P. 07360, MexicoDepartment of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico City C.P. 07360, MexicoDepartment of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico City C.P. 07360, MexicoDepartment of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico City C.P. 07360, MexicoGap 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.https://www.mdpi.com/1422-0067/22/1/358gap junctionsouabaincancer |
| spellingShingle | Mauricio Serrano-Rubi Lidia Jimenez Jacqueline Martinez-Rendon Marcelino Cereijido Arturo Ponce Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells International Journal of Molecular Sciences gap junctions ouabain cancer |
| title | Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells |
| title_full | Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells |
| title_fullStr | Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells |
| title_full_unstemmed | Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells |
| title_short | Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells |
| title_sort | ouabain promotes gap junctional intercellular communication in cancer cells |
| topic | gap junctions ouabain cancer |
| url | https://www.mdpi.com/1422-0067/22/1/358 |
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