Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?
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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 th...e 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.
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Oxidative Medicine and Cellular Longevity, 2021, 2021, e7753857-Publisher:
- Hindawi
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Institut za medicinska istraživanjaTY - JOUR AU - Kapor, Sunčica AU - Čokić, Vladan AU - Santibanez, Juan PY - 2021 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1174 AB - 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. PB - Hindawi T2 - Oxidative Medicine and Cellular Longevity T1 - Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection? SP - e7753857 VL - 2021 DO - 10.1155/2021/7753857 ER -
@article{ author = "Kapor, Sunčica and Čokić, Vladan and Santibanez, Juan", year = "2021", abstract = "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.", publisher = "Hindawi", journal = "Oxidative Medicine and Cellular Longevity", title = "Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?", pages = "e7753857", volume = "2021", doi = "10.1155/2021/7753857" }
Kapor, S., Čokić, V.,& Santibanez, J.. (2021). Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?. in Oxidative Medicine and Cellular Longevity Hindawi., 2021, e7753857. https://doi.org/10.1155/2021/7753857
Kapor S, Čokić V, Santibanez J. Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?. in Oxidative Medicine and Cellular Longevity. 2021;2021:e7753857. doi:10.1155/2021/7753857 .
Kapor, Sunčica, Čokić, Vladan, Santibanez, Juan, "Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?" in Oxidative Medicine and Cellular Longevity, 2021 (2021):e7753857, https://doi.org/10.1155/2021/7753857 . .