CYTOTOXIC EFFECTS AND MULTIDRUG RESISTANCE MODULATION BY FIVE BENZOPHENONES AND A XANTHONE ISOLATED FROM HYPERICUM ANNULATUM MORIS SUBSP ANNULATUM

The antiproliferative and cytotoxic effects of 5 natural benzophenones and a xanthone - gentisein, isolated from the aerial parts of Hypericum annulatum, were assessed using the MTT-dye reduction assay after 96 h exposure. The pharmacological screening was carried out in a panel of human tumor cell lines: HL-60 (acute promyelocyte leukemia), HL-60/Dox (selected in doxorubicin-containing medium; characterized by over-expression of MRP-1 and mdr phenotype), and K-562 (chronic myeloid leukemia). The tested polyphenols exhibited concentration-dependent cytotoxicity, whereby gentisein proved to exert the highest relative potency. A pharmacodynamic study for genomic DNA fragmentation was conducted, which has shown that the effects of the polyphenols are mediated by induction of programmed cell death. When applied at sub-cytotoxic concentrations, the investigated benzophenones and gentisein increased the chemosensitivity of HL-60/Dox cells to the anthracyclines doxorubicin, eprirubicin, idarubicin and daunorubicin. These findings indicate that the tested compounds could be considered promising as multidrug resistance modulators for testing in further; more detailed investigations. Biotechnol. & Biotechnol. Eq. 2013, 27(1), 3561-3568