Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser15, caspase dependent ceramide production and apoptosis in human leukemic cells

Faisal Thayyullathil; Shahanas Chathoth; Jaleel Kizhakkayil; Alaa Galadari; Abdulkader Hago; Mahendra Patel; Sehamuddin Galadari

doi:10.1016/j.bbrc.2011.05.156

Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser¹⁵, caspase dependent ceramide production and apoptosis in human leukemic cells

Faisal Thayyullathil, Shahanas Chathoth, Jaleel Kizhakkayil, Alaa Galadari, Abdulkader Hago, Mahendra Patel, Sehamuddin Galadari

Department of Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	1-6
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	411
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2011.05.156
Publication status	Published - Jul 22 2011

Keywords

Apoptosis
Caspase
Ceramide
Doxorubicin
GSH
P53
P53Ser

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2011.05.156

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Thayyullathil, F., Chathoth, S., Kizhakkayil, J., Galadari, A., Hago, A., Patel, M., & Galadari, S. (2011). Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser¹⁵, caspase dependent ceramide production and apoptosis in human leukemic cells. Biochemical and Biophysical Research Communications, 411(1), 1-6. https://doi.org/10.1016/j.bbrc.2011.05.156

Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser¹⁵, caspase dependent ceramide production and apoptosis in human leukemic cells. / Thayyullathil, Faisal; Chathoth, Shahanas; Kizhakkayil, Jaleel et al.
In: Biochemical and Biophysical Research Communications, Vol. 411, No. 1, 22.07.2011, p. 1-6.

Research output: Contribution to journal › Article › peer-review

Thayyullathil, F, Chathoth, S, Kizhakkayil, J, Galadari, A, Hago, A, Patel, M & Galadari, S 2011, 'Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser¹⁵, caspase dependent ceramide production and apoptosis in human leukemic cells', Biochemical and Biophysical Research Communications, vol. 411, no. 1, pp. 1-6. https://doi.org/10.1016/j.bbrc.2011.05.156

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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 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.",

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