Inhibitory effects of myricetin on mammalian DNA polymerase, topoisomerase and human cancer cell proliferation

► Myricetin was the strongest DNA polymerase inhibitor amongst the bioflavonoids tested. ► Myricetin was a selective inhibitor of mammalian DNA polymerase and topoisomerase. ► Myricetin suppressed the proliferation of cultured human colon cancer cells, HCT116. ► Myricetin halted the cell cycle in G2/M phase and induced apoptosis in HCT116 cells. ► Myricetin may exert its anticancer activity through DNA topoisomerase II inhibition. In this study, the inhibitory activities against mammalian DNA polymerases (pols) of 16 major bioflavonoids were investigated. Myricetin (3,3′,4′,5,5′,7-hexahydroxyflavone) was the most potent inhibitor of pols amongst the compounds tested, with IC50 values of 21.3–40.9μM. This compound did not affect the activities of plant (cauliflower) pol α or prokaryotic pols. Myricetin also inhibited human DNA topoisomerase II (topo II) activity with an IC50 value of 27.5μM, but did not inhibit the activities of other DNA metabolic enzymes tested. Myricetin also did not influence the direct binding to double stranded DNA as determined by thermal transition analysis. It was found to prevent the proliferation of human colon HCT116 carcinoma cells with an LD50 of 28.2μM, halt the cell cycle in G2/M phase, and induce apoptosis. These results suggest that the decrease of proliferation may be a result of the inhibition of cellular topoisomerase (topo) II rather than pols.