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

Author(s): Sezgi Kipcak, Buket Ozel, Cigir Biray Avci*, Leila S. Takanlou, Maryam S. Takanlou, Cumhur Gunduz, Nur Selvi Gunel

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 21 , Issue 13 , 2021


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Abstract:

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.

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

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Article Details

VOLUME: 21
ISSUE: 13
Year: 2021
Page: [1724 - 1731]
Pages: 8
DOI: 10.2174/1871520620666201106085929
Price: $95

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