A comparative study of the cytotoxic and genotoxic effects of ICRF-154 and bimolane, two catalytic inhibitors of topoisomerase II

Concentration-response studies of the chromosome-damaging effects of topoisomerase II inhibitors determined in vitro using human TK6 cells

“…While the clastogenic effects induced by the catalytic inhibitors seen here are in agreement with previously reported findings, the mechanism by which chromosome breaks occur for the catalytic inhibitors is not as well understood (7)(8)(25)(26)(27)(28)(29). Compounds such as ICRF −154 and ICRF−187 are believed to trap topo II in a "closed-clamp" formation where the double strand break has been properly ligated and the enzyme is no longer covalently bound to the DNA.…”

“…Topo II poisons, such as etoposide, act to stabilize the cleavage complex and inhibit the religation step, an important step leading to the formation of unprotected double stranded breaks. Catalytic inhibitors, on the other hand, affect other parts of the topo II catalytic cycle and do not directly stabilize the cleavage complex, though have been shown to have clastogenic effects in vitro and in vivo (6)(7)(8).…”

Arsenic trioxide-based therapy is suitable for patients with psoriasis-associated acute promyelocytic leukemia – A retrospective clinical study

“…10 These features make bimolane a potential genotoxic, cytotoxic, and leukemogenic agent. 9 Wang et al 1 confirmed that nonrecurrent chromosomal abnormalities were more frequent in patients with psoriasis-associated APL and a history of bimolane treatment than in those without bimolane treatment.…”

“…Frantz et al 7 found that bimolane had significant inhibitory effects on topoisomerase II. Studies have revealed that bimolane exhibited forceful mutagenicity, which could induce chromosomal breakage and aberrations in cultured human lymphocytes 8,9 and mouse bone marrow cells. 10 These features make bimolane a potential genotoxic, cytotoxic, and leukemogenic agent.…”

Anticancer Drug Combinations, A Big Momentum is Needed

“…More structural revisions by medicinal chemistry comparisons or even counteract by other types of drugs may enjoy great successes. Best example is the combinations of anthrocyclines such as doxorubicin with bisdioxopiperazine compounds (Biz) such as razoxane [12][13][14][15] and probimane [16][17][18][19]. More interestingly, doxorubicin and Biz compounds could cooperate one and another in combating with drug-resistance and neoplasm metastasis [12,13,16,17].…”