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

Biology

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

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 (US)
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
State	Published - Jul 22 2011

Keywords

Apoptosis
Caspase
Ceramide
Doxorubicin
GSH
P53
P53Ser

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2011.05.156

Cite this

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

@article{717135ca102e446b85942ae8f71649b2,

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 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.",

keywords = "Apoptosis, Caspase, Ceramide, Doxorubicin, GSH, P53, P53Ser",

author = "Faisal Thayyullathil and Shahanas Chathoth and Jaleel Kizhakkayil and Alaa Galadari and Abdulkader Hago and Mahendra Patel and Sehamuddin Galadari",

note = "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).",

year = "2011",

month = jul,

day = "22",

doi = "10.1016/j.bbrc.2011.05.156",

language = "English (US)",

volume = "411",

pages = "1--6",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

number = "1",

}

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

UR - http://www.scopus.com/inward/record.url?scp=79960565704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960565704&partnerID=8YFLogxK

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 -