Hydroxyurea and cellular senescence in non-transformed cells.

Hydroxyurea (HU) is a growth-inhibiting agent used to treat conditions characterized by excessive cellular proliferation. As an antimetabolite, HU inhibits ribonucleotide reductase, reducing the deoxyribonucleotide pool and thereby slowing DNA synthesis. Pharmacological inhibition of cell division is closely associated with the development of a cellular senescence phenotype, which may contribute to therapeutic resistance and tumor-associated inflammation. This phenotype has extensive effects, potentially inducing bystander effects and fostering tumor immunosuppression, thereby increasing the risk of cancer recurrence or relapse. Furthermore, HU has been shown to induce cellular senescence in non-malignant cells in laboratory settings. This review examines the principal molecular mechanisms underlying HU's cytotoxic and genotoxic effects, as well as the salient features of cellular senescence induction. A comprehensive understanding of the pathways through which HU prompts cellular senescence in normal cells may enhance current chemotherapy strategies and mitigate adverse effects in patients with cancer and other pathologies.