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Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?

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2021
Mechanisms_of_Hydroxyurea-Induced_Cellular_Senescence_pub_2021.pdf (1.218Mb)
Authors
Kapor, Sunčica
Čokić, Vladan
Santibanez, Juan
Article (Published version)
Metadata
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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 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.

Source:
Oxidative Medicine and Cellular Longevity, 2021, 2021, e7753857-
Publisher:
  • Hindawi
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200015 (University of Belgrade, Institute for Medical Research) (RS-200015)

DOI: 10.1155/2021/7753857

ISSN: 1942-0900

[ Google Scholar ]
URI
http://rimi.imi.bg.ac.rs/handle/123456789/1174
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
Institut za medicinska istraživanja
TY  - 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 . .

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