Docetaxel enhances the cytotoxic effects of imatinib on Philadelphia positive human chronic myeloid leukemia cells


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GUCLULER G., Baran Y.

HEMATOLOGY, cilt.14, ss.139-144, 2009 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 14 Konu: 3
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1179/102453309x426164
  • Dergi Adı: HEMATOLOGY
  • Sayfa Sayısı: ss.139-144

Özet

Chronic myelogenous leukemia (CML) results from a translocation between chromosomes 9 and 22 which generates BCR/ABL fusion protein and characterized by uncontrolled proliferation of immature white blood cells. Imatinib, a molecularly targeting anticancer agent, is used widely for the treatment of CML and showed significant activity in chronic and accelerated phases but much less in blast crisis phase. The resistance to imatinib especially in blast crisis phase is recognized as a major problem in the treatment of CML patients. Docetaxel is shown to arrest cells in G2/M phase of the cell cycle which makes cells more sensitive to chemo- and radiotherapy. In this study, we aimed to increase chemosensitivity of human K562 CML cells to imatinib in combination with docetaxel. Taken together, our results showed that the combination of imatinib and docetaxel decreased cellular proliferation and increased apoptosis in human K562 chronic myeloid leukemia cells as compared to any agent alone. Imatinib and docetaxel induced apoptosis through caspase-3 enzyme activity and mitochondrial membrane potential.