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Cellular thiols and reactive oxygen species in drug-induced apoptosis.
J Pharmacol Exp Ther. 2001 Jan; 296(1):1-6.JP

Abstract

In higher eukaryotes, reactive oxygen species (ROS) are generated during respiration in mitochondria in the course of reduction of molecular oxygen as well as by distinct enzyme systems. ROS have been implicated in the regulation of diverse cellular functions including defense against pathogens, intracellular signaling, transcriptional activation, proliferation, and apoptosis. The reduction-oxidation (redox) state of the cell is primarily a consequence of the precise balance between the levels of ROS and endogenous thiol buffers present in the cell, such as glutathione and thioredoxin, which protect cells from oxidative damage. Dramatic elevation of ROS, exceeding compensatory changes in the level of the endogenous thiol buffers, may result in the sustained activation of signaling pathways and expression of genes that induce apoptosis in affected cells. Many cytotoxic drugs function selectively to kill cancer cells by the abrogation of proliferative signals, leading to cell death, and numerous reports have demonstrated that ROS are generated following treatment with these drugs. In this review, we will summarize recent contributions to our understanding of the importance of cytotoxic drug-induced modulation of cellular redox status for signaling and transcription leading to activation of apoptotic effector mechanisms.

Authors+Show Affiliations

Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

11123355

Citation

Davis, W, et al. "Cellular Thiols and Reactive Oxygen Species in Drug-induced Apoptosis." The Journal of Pharmacology and Experimental Therapeutics, vol. 296, no. 1, 2001, pp. 1-6.
Davis W, Ronai Z, Tew KD. Cellular thiols and reactive oxygen species in drug-induced apoptosis. J Pharmacol Exp Ther. 2001;296(1):1-6.
Davis, W., Ronai, Z., & Tew, K. D. (2001). Cellular thiols and reactive oxygen species in drug-induced apoptosis. The Journal of Pharmacology and Experimental Therapeutics, 296(1), 1-6.
Davis W, Ronai Z, Tew KD. Cellular Thiols and Reactive Oxygen Species in Drug-induced Apoptosis. J Pharmacol Exp Ther. 2001;296(1):1-6. PubMed PMID: 11123355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular thiols and reactive oxygen species in drug-induced apoptosis. AU - Davis,W,Jr AU - Ronai,Z, AU - Tew,K D, PY - 2000/12/21/pubmed PY - 2001/3/3/medline PY - 2000/12/21/entrez SP - 1 EP - 6 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 296 IS - 1 N2 - In higher eukaryotes, reactive oxygen species (ROS) are generated during respiration in mitochondria in the course of reduction of molecular oxygen as well as by distinct enzyme systems. ROS have been implicated in the regulation of diverse cellular functions including defense against pathogens, intracellular signaling, transcriptional activation, proliferation, and apoptosis. The reduction-oxidation (redox) state of the cell is primarily a consequence of the precise balance between the levels of ROS and endogenous thiol buffers present in the cell, such as glutathione and thioredoxin, which protect cells from oxidative damage. Dramatic elevation of ROS, exceeding compensatory changes in the level of the endogenous thiol buffers, may result in the sustained activation of signaling pathways and expression of genes that induce apoptosis in affected cells. Many cytotoxic drugs function selectively to kill cancer cells by the abrogation of proliferative signals, leading to cell death, and numerous reports have demonstrated that ROS are generated following treatment with these drugs. In this review, we will summarize recent contributions to our understanding of the importance of cytotoxic drug-induced modulation of cellular redox status for signaling and transcription leading to activation of apoptotic effector mechanisms. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/11123355/Cellular_thiols_and_reactive_oxygen_species_in_drug_induced_apoptosis_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11123355 DB - PRIME DP - Unbound Medicine ER -