Topoisomerase Inhibitors in Cancer
Topoisomerases are nuclear enzymes involved in DNA replication, transcription, chromosomal segregation, and recombination. There are two types of topoisomerases found in all cells: type I enzymes that cut single-stranded DNA and type II enzymes that cut and pass double-stranded DNA. Topo2 is involved in endoreduplication as well as mitotic chromosomal segregation following replication. Inhibiting topo2 in cells may cause a cascade of events ranging from endoreduplication and polyploidy to cell death. Etoposide is employed as an anticancer drug by targeting the topo2-DNA complex, however, its induction of the DNA strand break-stable complex may result in chromosomal translocation and, ultimately, a particular kind of leukaemia. There are two types of topoisomerase 2 inhibitors. Class 1 chemicals, such as etoposide and doxorubicin, are known as classical poisons because they stabilise the DNA-Topo 2 complex by producing lesions with broken DNA strands and protein covalently bound to them...