The contribution of plukenetione A to the anti-tumoral activity of Cuban propolis.

Increasing efforts are directed toward finding applications for natural products and their derivatives in the treatment of human diseases. Among such products, propolis, a resinous substance produced by honey bees from various plant sources, has been found to be a promising source of potential therapeutics. In the present work, we aimed at studying the perspective of Cuban propolis as a source of possible anti-cancer agents. We found an anti-metastatic effect in mice and considerable cytotoxicity without cross-resistance in both wild-type and chemoresistant human tumor cell lines. Plukenetione A--identified for the first time in Cuban propolis--induced G0/G1 arrest and DNA fragmentation in colon carcinoma cells. Furthermore, the activities of both topoisomerase I and DNA polymerase were inhibited, while the expression of topoisomerase II-beta, EGF receptor, and multidrug resistance-related protein genes was found repressed. We assume that plukenetione A contributes to the anti-tumoral effect of Cuban propolis mainly by targeting topoisomerase I as well as DNA polymerase.