Effect of Dasatinib on Genes Related to Mitotic Catastrophe Pathway in Chronic Myeloid Leukemia Cells

Author(s):

Sezgi Kipcak, Buket Ozel, Cigir B. Avci*, Leila S. Takanlou, Maryam S. Takanlou, Cumhur Gunduz and Nur S. Gunel   Pages 1724 - 1731 ( 8 )

Abstract:

<P>Background: Chronic Myeloid Leukemia (CML) is characterized by a reciprocal translocation t(9;22) and forms BCR/ABL1 fusion gene called the Philadelphia chromosome. The therapeutic targets for CML patients mediated with BCR/ABL1 oncogenic are tyrosine kinase inhibitors such as imatinib, dasatinib, and nilotinib. The latter two of which have been approved for the treatment of imatinib-resistant or intolerance CML patients. Mitotic Catastrophe (MC) is one of the non-apoptotic mechanisms initiated in types of cancer cells in response to anti-cancer therapies. Pharmacological inhibitors of G2 checkpoint members or genetic suppression of PLK1, PLK2, ATR, ATM, CHK1, and CHK2 can trigger DNA-damage-stimulated mitotic catastrophe. PLK1 and AURKA/B are anomalously expressed in CML cells, where phosphorylation and activation of PLK1 occur by AURKB at centromeres and kinetochores. </P><P> Objective: The purpose of this study is to investigate the effect of dasatinib on the expression of genes in MC and apoptosis pathways in K562 cells. </P><P> Methods: Total RNA was isolated from K-562 cells treated with the IC₅₀ value of dasatinib and untreated cells as a control group. The expression of MC and apoptosis-related genes, was analyzed by the qRT-PCR system. </P><P> Results: The array-data demonstrated that dasatinib-treated K562 cells significantly caused the decrease of several genes (AURKA, AURKB, PLK, CHEK1, MYC, XPC, BCL2, and XRCC2). </P><P> Conclusion: The evidence supplies a basis to support clinical researches for the suppression of oncogenes such as PLKs with AURKs in the treatment of types of cancer, especially chronic myeloid leukemia.</P>

Keywords:

Mitotic catastrophe, apoptosis, CML, BCR-ABL, dasatinib, AURK, PLK.

Affiliation:

Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir, Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir, Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir, Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir, Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir, Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir, Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir

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