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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume411
Issue number1
DOIs
StatePublished - 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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