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Effect of Dasatinib on Genes Related to Mitotic Catastrophe Pathway in Chronic Myeloid Leukemia Cells
Sezgi Kipcak1, Buket Ozel1, Cigir B Avci1
1Deparment of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey.
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.
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.
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.
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).
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.
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