Impact of Oxidative Metabolism on the Cytotoxic and Genotoxic Potential of Genistein in Human Colon Cancer Cells.

Scope: Genistein (GEN) is known to be genotoxic via targeting topoisomerase-II (TOPII). Oxidative metabolism of GEN is shown to generate hydroxylated metabolites with catecholic structures. The present study focuses on the impact of oxidative metabolism of GEN, exemplified for 3'-hydroxygenistein (3'-OH-GEN) and 6-hydroxygenistein (6-OH-GEN), on topoisomerase interference and the resulting genotoxic potential in HT-29 human colon carcinoma cells.

Methyleugenol and oxidative metabolites induce DNA damage and interact with human topoisomerases.

Methyleugenol is a substituted alkenylbenzene found in several herbs and spices. It is classified by the European Union's Scientific Committee on Food as a genotoxic carcinogen. We addressed the biological mechanism of the genotoxic properties of methyleugenol and its oxidative metabolites.

Inhibition of topoisomerase II by phase II metabolites of resveratrol in human colon cancer cells.

Scope: The cytotoxic and genotoxic potential of phase II metabolites of resveratrol (RSV) was investigated in human colon cells with special emphasis on human topoisomerase (TOP) II.

Methods And Results: Cell-free screening of topoisomerase II (TOPII) inhibition by the decatenation assay showed inhibitory potential for RSV (≥200 μM) and for the first time for the three human phase II metabolites RSV-3-sulfate (≥200 μM), RSV-3-glucuronide (≥100 μM) and RSV-disulfate (≥100 μM). Conjugation at the C4'-position (RSV-4'-sulfate and RSV-4'-glucuronide) resulted in loss of the inhibitory potential in this assay.

Resveratrol modulates the topoisomerase inhibitory potential of doxorubicin in human colon carcinoma cells.

Resveratrol (RSV) is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II) poison doxorubicin (DOX).

Oxidative metabolism enhances the cytotoxic and genotoxic properties of the soy isoflavone daidzein.

Scope: Oxidative metabolism of daidzein (DAI) might result in the formation of hydroxylated metabolites. Here, we address the question whether these metabolites differ in their biological activity from the parent isoflavone, exemplified for the epidermal growth factor receptor and topoisomerase II, potentially resulting in an enhanced toxic profile.

Methods And Results: In contrast to DAI, 6-hydroxydaidzein (6-HO-DAI) and 8-hydroxydaidzein (8-HO-DAI) were found to inhibit the tyrosine kinase activity of the epidermal growth factor receptor in an ELISA-based test system, but showed no effects within cells.

Topoisomerase II-targeting properties of a grapevine-shoot extract and resveratrol oligomers.

Grapevine-shoot extracts (GSE), containing trans-resveratrol and resveratrol oligomers, are commercially available as food supplements. Considering the topoisomerase-targeting properties of trans-resveratrol, the question of whether GSE affect these enzymes, thereby potentially causing DNA damage, was addressed. In a decatenation assay, GSE potently suppressed the catalytic activity of topoisomerase IIα (≥5 μg/mL).