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, cilt.137, sa.10, ss.1535-1544, 2011 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 137 Sayı: 10
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1007/s00432-011-1016-y
  • Dergi Adı: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1535-1544
  • Anahtar Kelimeler: Ceramide, Apoptosis, Glucosylceramide, Drug resistance, CML, INDUCED APOPTOSIS, SPHINGOSINE KINASE-1, INHIBITION, MECHANISM, SPHINGOLIPIDS, EXPRESSION, CARCINOMA, STRESS, DEATH
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

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.