There is cumulative strong evidence that diets rich in flavanols can provide certain positive health benefits, particularly with respect to the cardiovascular system. Consequently, it has been suggested that increasing one's dietary intake of flavanols may be of benefit. Complicating this idea, there are reports that high intakes of certain
flavonoids during pregnancy are associated with an increased risk for acute infant
leukemia due to a
poison effect of select polyphenolic compounds on
DNA topoisomerase (
topo) II activity that promotes aberrant
chromosomal translocations. In the current study, we characterized the effects of select flavanols (
epicatechin and
catechin monomers), and select flavanol dimers and longer oligomers, on
topo II activity, and on cellular toxicity in vitro. In contrast to the chemotherapeutic
drug etoposide (
VP16) and the
flavonol quercetin, which strongly inhibited
topo II activity and increased the formation of cleavage complexes demonstrating a
poison effect, the flavanols
epicatechin and
catechin had little effect on
topo II
enzyme activity. Accordingly, several fold greater concentrations of the flavanols were required to achieve cellular toxicity similar to that of
quercetin and
VP16 in cultures of myeloid and lymphoid cells. Low cellular toxicity and limited
topo II inhibition were also observed with a
procyanidin-rich cocoa extract. Of all the flavanols tested, the dimers (B2, B5 and a mix of both) exerted the greatest inhibition of
topo II and inhibited cellular proliferation rates at concentrations similar to
quercetin. However, in contrast to
quercetin, the dimers did not function as
topo II
poisons. Collectively, our in vitro data show that cocoa-derived flavanols have limited effects on
topo II activity and cellular proliferation in
cancer cell lines. We predict that these compounds are likely to have limited leukemogenic potential at physiological concentrations.