Nitric oxide-donating aspirin induces G2/M phase cell cycle arrest in human cancer cells by regulating phase transition proteins.

International Journal of Oncology
Li Gao, Jennie L Williams

Abstract

NO-aspirin (NO-ASA), consisting of aspirin and a nitric oxide-releasing group, is safer than aspirin and effective in colon cancer prevention. Here, we examined the mechanism of action of NO-ASA by focusing primarily on its effects on the cell cycle. NO-ASA reduced the growth of several cell lines from colon, pancreas, skin, cervix and breast cancer much more potently than aspirin, with 24-h IC(50) values of 133-268 µM, while those of ASA were >1,000 µM. NO-ASA elevated the intracellular levels of reactive oxygen species, generating a state of oxidative stress. In all cell lines examined, NO-ASA induced cell cycle arrest in the G(2)/M phase transition accompanied by altered expression of G(2)/M transition-related proteins. In SW480 colon cancer cells NO-ASA modulated proteins controlling this transition. Thus, it markedly increased the levels of cyclin B1, decreased the expression of cyclin D1 and Cdc25C, and increased the Thr14/Tyr15-phosphorylation of Cdk1 while leaving unchanged its protein levels. These changes, including the G2/M arrest, were prevented by pretreating the cells with the anti-oxidant N-acetyl-cysteine, indicating that redox signaling is likely responsible for the cell cycle changes, a conclusion consistent w...Continue Reading

Citations

Jul 18, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Niharika NathKhosrow Kashfi
Aug 8, 2013·Biochimica Et Biophysica Acta·Chul-Woong PyoSang-Yun Choi
Oct 6, 2020·The Biochemical Journal·Salvatore Rizza, Giuseppe Filomeni
Dec 17, 2020·International Journal of Molecular Sciences·Faizan H KhanSharon A Glynn

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