Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation

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BARAN Y., Bielawski J., GÜNDÜZ U., Ogretmen B.

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, vol.137, no.10, pp.1535-1544, 2011 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 137 Issue: 10
  • Publication Date: 2011
  • Doi Number: 10.1007/s00432-011-1016-y
  • Journal Name: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1535-1544
  • Keywords: Ceramide, Apoptosis, Glucosylceramide, Drug resistance, CML, INDUCED APOPTOSIS, SPHINGOSINE KINASE-1, INHIBITION, MECHANISM, SPHINGOLIPIDS, EXPRESSION, CARCINOMA, STRESS, DEATH
  • Middle East Technical University Affiliated: Yes

Abstract

Purpose Drug resistance presents a major obstacle for the treatment of some patients with chronic myeloid leukemia (CML). Pro-apoptotic ceramide mediates imatinib-induced apoptosis, and metabolism of ceramide by glucosylceramide synthase (GCS) activity, converting ceramide to glucosyl ceramide, might contribute to imatinib resistance. In this study, we investigated the role of ceramide metabolism by GCS in the regulation of imatinib-induced apoptosis in drug-sensitive and drug-resistant K562 and K562/IMA-0.2 and K562/IMA-1 human CML cells, which exhibit about 2.3- and 19-fold imatinib resistance, respectively.