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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Bibliographic Details
Published in:Oncology letters 2021-04, Vol.21 (4), p.251, Article 251
Main Authors: Abdelghany, Lina, El-Mahdy, Nageh, Kawabata, Tsuyoshi, Goto, Shinji, Li, Tao-Sheng
Format: Article
Language:English
Subjects:
Adenosine
Analysis
Anthracyclines
Antibodies
Cancer
Cell growth
Chemotherapy
Colorectal cancer
Cyclic adenylic acid
Cytotoxicity
Dipyridamole
Drug dosages
Drug interactions
Experiments
Kinases
Laboratories
Lymphoma
Lymphomas
Monosaccharides
Oncology
Phosphorylation
Protein binding
Software
Stem cells
Sugars
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Summary: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.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2021.12512