Myricitrin Fromcombretum Lanceolatumexhibits Inhibitory Effect On Dna-Topoisomerase Type Ii Alpha And Protective Effect Againstin Vivodoxorubicin-Induced Mutagenicity

Flavonoids-compounds abundant in balanced daily diets-have been extensively investigated for biological activity. The pronounced antiproliferative effects of flavonoids have prompted studies to elucidate their mode of action against tumor cells. The anticancer properties of myricetin, a 3 ',4 ',5 '-tri-hydroxylated flavonol, have been confirmed for a number of neoplasms, but myricitrin, its 3-O-rhamnoside derivative found in fruits and other parts of edible plants, has been scarcely investigated as a chemopreventive agent. This study evaluated the antiproliferative potential of myricitrin obtained fromCombretum lanceolatum(Combretaceae) against MCF7 (breast), PC-3 (prostate), HT-29 (colon), 786-0 (kidney), and HL-60 (acute promyelocytic leukemia) cancer cell lines, using the sulforhodamine B and tetrazolium salt assays. Myricitrin proved most effective in inhibiting growth of HL-60 cells (GI(50) = 53.4 mu mol center dot L-1), yet showed weak antiproliferative activity against other cell lines. Possible cytotoxic mechanisms involving inhibition of topoisomerases I and II alpha by myricitrin were also evaluated, revealing inhibitory activity only against topoisomerase II alpha. The results suggested that topoisomerase II alpha inhibition is the probable mechanism responsible for the antiproliferative activity of myricitrin.In vivomutagenicity by myricitrin and its possible antimutagenic effect on doxorubicin-induced DNA damage were also investigated by performing the somatic mutation and recombination test (SMART) onDrosophila melanogaster. Myricitrin proved nonmutagenic to the offspring of standard (ST) and high-bioactivation (HB) crosses, while cotreatments with doxorubicin revealed the antimutagenic properties of myricitrin, even under conditions of high metabolic activation.