Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation

Abdelghany,Lina; El-Μahdy,Nageh; Kawabata,Tsuyoshi; Goto,Shinji; Li,Tao-Sheng

doi:10.3892/ol.2021.12512

Dipyridamole induces the phosphorylation of CREB to promote cancer cell proliferation

Authors:
- Lina Abdelghany
- Nageh El-Μahdy
- Tsuyoshi Kawabata
- Shinji Goto
- Tao-Sheng Li
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Affiliations: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
Published online on: February 3, 2021 https://doi.org/10.3892/ol.2021.12512
Article Number: 251
Copyright: © Abdelghany et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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