Inhibitory effects of a major soy isoflavone, genistein, on human DNA topoisomerase II activity and cancer cell proliferation

Abstract

The inhibitory activity of 3 soy isoflavones (daidzein, genistein and glycitein) and their glycosides (daidzin, genistin and glycitin) on mammalian DNA polymerases (pols) and topoisomerases (topos) was investigated. Of the compounds tested, only genistein selectively inhibited human topo II activity and had an IC50 value of 37.5 µM. These isoflavones had no effect on the activity of human topo I; mammalian pols α, β, γ and κ; or on any other DNA metabolic enzyme tested. Thermal transition analysis indicated that genistein did not influence the direct binding to double-stranded DNA. Genistein prevented the proliferation of HCT116 human colon carcinoma cells with an LD50 of 94.0 µM and it halted the cell cycle in G2/M phase. These results suggest that decreases in cell proliferation due to genistein may result from the inhibition of cellular topo II and that genistein, a major soy isoflavone, may be an anticancer food component. The relationship between the structures and these bioactivities of soy isoflavones is discussed.

Determination of Major Isoflavones in Soy Drinks by Solid-Phase Micro Extraction Coupled to Liquid Chromatography

“…Despite their declared utility, evidence of increased risks to human health, mainly due to their estrogenic activity affecting numerous physiological responses, are also reported in the literature (Andres et al 2011;Anderson et al 2013). Isoflavones have topoisomerase II inhibition capacity that is related to the occurrence of mutations (Mizushina et al 2013). Therefore, the consumption of isoflavones is currently under control, and it has been recently limited after consumer concern.…”

Determination of Isoflavones in Soybean Flour by Matrix Solid-Phase Dispersion Extraction and Liquid Chromatography with UV-Diode Array Detection

“…A typical chromatogram relevant to the analysis of a soybean flour sample extract is shown in Figure 2. As can be seen, the peaks of the detected analytes were yet again well resolved, with no significant interference from matrix compounds, with the only exception of glycitin, which was never detected in any of the analyzed samples according to literature data [11,12]. Each chromatographic peak was confirmed by its retention time and the spectra overlaying technique.…”

“…Previous investigations have shown that genistein and its aglycone are the predominant isoflavones in soybean [10,11]. Genistein is a specific inhibitor of human DNA topoisomerase II and may possess anticancer activity [12].…”

Polytrichum commune L.ex Hedw ethyl acetate extract-triggered perturbations in intracellular Ca2+ homeostasis regulates mitochondrial-dependent apoptosis

“…Crude extracts or components isolated from plants are important sources to screen as cancer chemotherapy, such as genistein and resveratrol (Dorai and Aggarwal, 2004;Mizushina et al, 2013;Singh et al, 2014).…”