title: Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser¹⁵, caspase dependent ceramide production and apoptosis in human leukemic cells.
abstract: Glutathione (GSH) is the most abundant non-protein antioxidant in mammalian cells. It has been implicated in playing an important role in different signal transduction pathways, and its depletion is an early hallmark in the progression of apoptosis in response to a number of proapoptotic stimuli. We have selectively investigated the role of GSH in cytotoxic response of Jurkat and Molt-4 human leukemic cells to the anti-cancer drug Doxorubicin. In this study, we have shown that extracellular supplementation of GSH to human leukemic cells renders them a resistant phenotype to Doxorubicin treatment. Glutathione pre-treatment inhibits Doxorubicin-induced p53Ser(15) phosphorylation, caspase dependent ceramide (Cer) generation, Poly (ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation. Taken together, these results indicate that the major cellular antioxidant GSH influences the chemotherapeutic efficacy of Doxorubicin towards human leukemic cells.
authors.affiliation: Cell Signaling Laboratory, Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al Ain, United Arab Emirates.
authors.forename: Faisal
authors.initials: F
authors.lastname: Thayyullathil
authors.forename: Shahanas
authors.initials: S
authors.lastname: Chathoth
authors.forename: Jaleel
authors.initials: J
authors.lastname: Kizhakkayil
authors.forename: Alaa
authors.initials: A
authors.lastname: Galadari
authors.forename: Abdulkader
authors.initials: A
authors.lastname: Hago
authors.forename: Mahendra
authors.initials: M
authors.lastname: Patel
authors.forename: Sehamuddin
authors.initials: S
authors.lastname: Galadari
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis*; D004317:Doxorubicin / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism*; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D002518:Ceramides; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D020169:Caspases; D005978:Glutathione