Inhibitory effects of a major soy isoflavone, genistein, on human DNA topoisomerase II activity and cancer cell proliferation
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...
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| Published in | International journal of oncology Vol. 43; no. 4; pp. 1117 - 1124 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Greece
D.A. Spandidos
01.10.2013
Spandidos Publications UK Ltd |
| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | 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. 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. |
| Author | SHIOMI, KAZUAKI MIZUSHINA, YOSHIYUKI KURIYAMA, ISOKO YOSHIDA, HIROMI TAKAHASHI, YOSHIHIRO |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23900272$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | anticancer Cancer cancer cell proliferation cell cycle arrest Cell Cycle Checkpoints - drug effects Cell Division - drug effects Cell Proliferation - drug effects Colonic Neoplasms - drug therapy Colonic Neoplasms - enzymology Colonic Neoplasms - pathology DNA topoisomerase II DNA Topoisomerases, Type II - biosynthesis DNA Topoisomerases, Type II - chemistry DNA Topoisomerases, Type II - genetics enzyme inhibitor genistein Genistein - administration & dosage Genistein - chemistry Glycine max - chemistry HCT116 Cells Humans Isoflavones - administration & dosage Isoflavones - chemistry Kinases Protein Conformation - drug effects soy isoflavones Soy products Soybeans Structure-Activity Relationship |
| Title | Inhibitory effects of a major soy isoflavone, genistein, on human DNA topoisomerase II activity and cancer cell proliferation |
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