In addition to cell cycle regulation, topoisomerase has
been shown to be another major target of antiproliferative
agents (1013). The chemotherapeutic drug etoposide
kills cancer cells by stabilitating the transient intermediate
cleavage complex. The resulting accumulation of cleavage
complexes could lead to the formation of permanent
DNA strand breaks that fragment the genome leading
to the activation of death pathways (56). In addition,
apoptosis has been shown to be the most effective
death-pathway in tumor cells subsequent to the inhibition
of topoisomerase II (57). Our findings document that
2-MCA suppressed topoisomerase I as well as II activities
in a dose-dependent fashion (Fig. 6), which, in part, may
be a mechanism leading the cells to apoptosis. While
most of topoisomerase inhibitors are selectively targeting
either topoisomerase I or II (58), our results clearly
demonstrate that 2-MCA suppressed topoisomerase I as
well as II activities in COLO 205 cells.