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Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation

Dipyridamole, a traditional anti-platelet drug, has been reported to inhibit the proliferation of cancer cells. The present study aimed to investigate the possibility of dipyridamole as an adjuvant of chemotherapy by enhancing the cytotoxicity of an anti-cancer drug. The cytotoxicity of colorectal c...

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Autores principales: Abdelghany, Lina, El-Mahdy, Nageh, Kawabata, Tsuyoshi, Goto, Shinji, Li, Tao-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882894/
https://www.ncbi.nlm.nih.gov/pubmed/33664815
http://dx.doi.org/10.3892/ol.2021.12512
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author Abdelghany, Lina
El-Mahdy, Nageh
Kawabata, Tsuyoshi
Goto, Shinji
Li, Tao-Sheng
author_facet Abdelghany, Lina
El-Mahdy, Nageh
Kawabata, Tsuyoshi
Goto, Shinji
Li, Tao-Sheng
author_sort Abdelghany, Lina
collection PubMed
description Dipyridamole, a traditional anti-platelet drug, has been reported to inhibit the proliferation of cancer cells. The present study aimed to investigate the possibility of dipyridamole as an adjuvant of chemotherapy by enhancing the cytotoxicity of an anti-cancer drug. The cytotoxicity of colorectal cancer cells (HCT-8), CD133(+)/CD44(+) stem-like subpopulation of HCT-8 cells and lymphoma cells (U937) to dipyridamole and/or doxorubicin was evaluated using MTT proliferation and colony forming assays. The expression levels of phosphorylated cAMP-regulatory element-binding protein (pCREB) and poly(ADP-ribose) polymerase-1 (PARP-1) in cells were analyzed via western blotting and immunofluorescence. The present study reported controversial data regarding the anti-cancer effect of dipyridamole. Dipyridamole increased, rather than inhibited, the proliferation of HCT-8 and U937 cells in a dose-dependent manner. Furthermore, it was found that dipyridamole significantly increased the expression levels of pCREB and PARP-1. However, the combined usage of dipyridamole significantly enhanced the cytotoxicity of doxorubicin to HCT-8 cells at particular doses. Based on the current findings, dipyridamole likely induces the phosphorylation of CREB to promote the proliferation of cancer cells, but may enhance the cytotoxicity of anti-cancer drugs at particular doses.
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spelling pubmed-78828942021-03-03 Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation Abdelghany, Lina El-Mahdy, Nageh Kawabata, Tsuyoshi Goto, Shinji Li, Tao-Sheng Oncol Lett Articles Dipyridamole, a traditional anti-platelet drug, has been reported to inhibit the proliferation of cancer cells. The present study aimed to investigate the possibility of dipyridamole as an adjuvant of chemotherapy by enhancing the cytotoxicity of an anti-cancer drug. The cytotoxicity of colorectal cancer cells (HCT-8), CD133(+)/CD44(+) stem-like subpopulation of HCT-8 cells and lymphoma cells (U937) to dipyridamole and/or doxorubicin was evaluated using MTT proliferation and colony forming assays. The expression levels of phosphorylated cAMP-regulatory element-binding protein (pCREB) and poly(ADP-ribose) polymerase-1 (PARP-1) in cells were analyzed via western blotting and immunofluorescence. The present study reported controversial data regarding the anti-cancer effect of dipyridamole. Dipyridamole increased, rather than inhibited, the proliferation of HCT-8 and U937 cells in a dose-dependent manner. Furthermore, it was found that dipyridamole significantly increased the expression levels of pCREB and PARP-1. However, the combined usage of dipyridamole significantly enhanced the cytotoxicity of doxorubicin to HCT-8 cells at particular doses. Based on the current findings, dipyridamole likely induces the phosphorylation of CREB to promote the proliferation of cancer cells, but may enhance the cytotoxicity of anti-cancer drugs at particular doses. D.A. Spandidos 2021-04 2021-02-03 /pmc/articles/PMC7882894/ /pubmed/33664815 http://dx.doi.org/10.3892/ol.2021.12512 Text en Copyright: © Abdelghany et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Abdelghany, Lina
El-Mahdy, Nageh
Kawabata, Tsuyoshi
Goto, Shinji
Li, Tao-Sheng
Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation
title Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation
title_full Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation
title_fullStr Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation
title_full_unstemmed Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation
title_short Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation
title_sort dipyridamole induces the phosphorylation of creb to promote cancer cell proliferation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882894/
https://www.ncbi.nlm.nih.gov/pubmed/33664815
http://dx.doi.org/10.3892/ol.2021.12512
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