TY - JOUR
T1 - Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser15, caspase dependent ceramide production and apoptosis in human leukemic cells
AU - Thayyullathil, Faisal
AU - Chathoth, Shahanas
AU - Kizhakkayil, Jaleel
AU - Galadari, Alaa
AU - Hago, Abdulkader
AU - Patel, Mahendra
AU - Galadari, Sehamuddin
N1 - Funding Information:
This work was financially supported by The Sheikh Hamdan Award for Medical Sciences (MRG-32-2007-2008), and in part grant from The Emirates Foundation (EF-2008/075).
PY - 2011/7/22
Y1 - 2011/7/22
N2 - 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 p53Ser15 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.
AB - 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 p53Ser15 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.
KW - Apoptosis
KW - Caspase
KW - Ceramide
KW - Doxorubicin
KW - GSH
KW - P53
KW - P53Ser
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U2 - 10.1016/j.bbrc.2011.05.156
DO - 10.1016/j.bbrc.2011.05.156
M3 - Article
C2 - 21669188
AN - SCOPUS:79960565704
SN - 0006-291X
VL - 411
SP - 1
EP - 6
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -