Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?
Sunčica KaporVladan P ČokićJuan Francisco SantibanezPublished in: Oxidative medicine and cellular longevity (2021)
Hydroxyurea (HU) is a water-soluble antiproliferative agent used for decades in neoplastic and nonneoplastic conditions. HU is considered an essential medicine because of its cytoreduction functions. HU is an antimetabolite that inhibits ribonucleotide reductase, which causes a depletion of the deoxyribonucleotide pool and dramatically reduces cell proliferation. The proliferation arrest, depending on drug concentration and exposure, may promote a cellular senescence phenotype associated with cancer cell therapy resistance and inflammation, influencing neighboring cell functions, immunosuppression, and potential cancer relapse. HU can induce cellular senescence in both healthy and transformed cells in vitro, in part, because of increased reactive oxygen species (ROS). Here, we analyze the main molecular mechanisms involved in cytotoxic/genotoxic HU function, the potential to increase intracellular ROS levels, and the principal features of cellular senescence induction. Understanding the mechanisms involved in HU's ability to induce cellular senescence may help to improve current chemotherapy strategies and control undesirable treatment effects in cancer patients and other diseases.
Keyphrases
- dna damage
- reactive oxygen species
- cell therapy
- oxidative stress
- endothelial cells
- cell proliferation
- stress induced
- induced apoptosis
- papillary thyroid
- water soluble
- diabetic rats
- stem cells
- cell death
- signaling pathway
- high glucose
- mesenchymal stem cells
- single cell
- young adults
- bone marrow
- emergency department
- climate change
- rectal cancer
- childhood cancer
- locally advanced
- heat shock