Selective killing of G2 decatenation checkpoint defective colon cancer cells by catalytic topoisomerase II inhibitor

Biochimica Et Biophysica Acta
Chetan Kumar JainHemanta Kumar Majumder

Abstract

Cancer cells with defective DNA decatenation checkpoint can be selectively targeted by the catalytic inhibitors of DNA topoisomerase IIα (topo IIα) enzyme. Upon treatment with catalytic topo IIα inhibitors, cells with defective decatenation checkpoint fail to arrest their cell cycle in G2 phase and enter into M phase with catenated and under-condensed chromosomes resulting into impaired mitosis and eventually cell death. In the present work we analyzed decatenation checkpoint in five different colon cancer cell lines (HCT116, HT-29, Caco2, COLO 205 and SW480) and in one non-cancerous cell line (HEK293T). Four out of the five colon cancer cell lines i.e. HCT116, HT-29, Caco2, and COLO 205 were found to be compromised for the decatenation checkpoint function at different extents, whereas SW480 and HEK293T cell lines were found to be proficient for the checkpoint function. Upon treatment with ICRF193, decatenation checkpoint defective cell lines failed to arrest the cell cycle in G2 phase and entered into M phase without proper chromosomal decatenation, resulting into the formation of tangled mass of catenated and under-condensed chromosomes. Such cells underwent mitotic catastrophe and rapid apoptosis like cell death and showed h...Continue Reading

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Citations

Apr 25, 2017·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Birgit JanickeKersti Alm
Aug 2, 2018·Cellular and Molecular Life Sciences : CMLS·Andreas Brown, Hartmut Geiger
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Nov 2, 2019·Genes·Joyce H Lee, James M Berger
Feb 28, 2020·World Journal of Gastroenterology : WJG·Shi-Tong WangLi-Xuan Sang

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