Background:
Chronic myeloid leukemia (CML), is characterized by a reciprocal translocation t(9;22) and forms the
BCR/ABL1 fusion gene, which is called the Philadelphia chromosome. The therapeutic targets for CML patients which are 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
which frequently 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, AURKA/B anomalously expressed in CML cells, that phosphorylation and activation of PLK1 occur by AURKB at centromeres
and kinetochores.
Objective:
The purpose of this study was 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 were 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 supply 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.
Selective cytotoxicity of vanadium complexes on human pancreatic ductal adenocarcinoma cell line by inducing necroptosis, apoptosis and mitotic catastrophe process
