Although generation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for anti-tumor activity, they make these drugs cardiotoxic.

The hydroxy‐9,10‐anthraquinones in anthracyclines form semiquinones and reactive oxygen species (ROS) that help in antitumor activity. ROS generation is cytotoxic to cells but cardiotoxic as well. Carminic acid (CA) with a sugar bound to a hydroxyanthraquinone resembles anthracyclines closely. Role of sugar in anthracyclines was realized from physicochemical parameters of CA that were found to be in between those of anthracyclines and hydroxy‐9,10‐anthraquinones. A Cu(II)complex of CA was prepared and its structure attempted from powder X‐ray diffraction. Studies with DNA revealed unlike CA, the complex did not show decrease in binding constant with increase in the pH of the medium. DNA relaxation assay showed the complex as a dual inhibitor of human DNA topoisomerase I and topoisomerase II stabilizing covalent topoisomerase‐DNA adducts in vitro. Inhibition of growth of ALL‐MOLT‐4 cells was higher for the complex supporting in vitro experiments. An enzyme assay revealed less superoxide formation for the complex suggesting that it might be less cardiotoxic. Decrease in superoxide for the complex does not affect anticancer activity, which was greater than CA.

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 higher sensitivity for ICRF193. Our study suggests that catalytic inhibitors of topoisomerase IIα are promising therapeutic agents for the treatment of colon cancers with defective DNA decatenation checkpoint.