Sulphur-containing non enzymatic antioxidants: therapeutic tools against cancer.
The prevention of oxidation is an essential process in all cells, as decreased antioxidant protection may lead to cytotoxicity, mutagenicity and carcinogenicity. The mechanisms by which oxidative stress contributes to carcinogenesis include modulation of gene expression and induction of genetic modifications. Cellular methylation and antioxidant metabolism are linked by the transsulfuration pathway, which converts the methionine cycle intermediate, homocysteine, to cysteine, the limiting reagent in glutathione synthesis. Taurine can protect cells from oxidant-induced injury scavenging strong oxidant and cytotoxic agents, and lipoic acid can regenerate glutathione. N-acetylcysteine has anticancer properties such as counteractions against mutagens and prevention of tumor progression. The oxidizing agents react with the thiol group of these non enzymatic antioxidants determining cellular redox potential, and modulating several biological events, since different redox-sensitive molecules are involved in many cell responses such as proliferation, growth arrest, and death. The high metabolic activity characteristic of cancer cells often upregulates oxidative stress protection mechanisms. In fact, glutathione depletion is an early hallmark observed in apoptosis and it has been demonstrated as a common feature of cancer.
Department of Biologia Molecular y Bioquimica, Facultad de Ciencias, Campus de Teatinos, Universidad de Malaga, Malaga, Spain. jmates@uma.es
Jose M
JM
Mates
Juan A
JA
Segura
Francisco J
FJ
Alonso
Javier
J
Marquez
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013457:Sulfur Compounds / Q000378:metabolism
D000975:Antioxidants; D013457:Sulfur Compounds; D005978:Glutathione