TY - JOUR AB - Low molecular weight (LMW) polyphenolics containing a polyhydroxylated benzyl moiety are abundant in medicinal plants. In the present study, we report on the activities of seven LMW polyphenolics isolated from Inonotus obliquus, a medicinal mushroom. The isolated compounds included caffeic acid (CA), 3,4-dihydroxybenzalacetone (DBL), gallic acid, syringic acid, protocatechuic acid, 3,4-dihydroxybenzaldehyde and 2,5-dihydroxyterephthalic acid. We analyzed their inhibitory effects on DNA polymerase (pol) and DNA topoisomerase (topo), and their effects on human cancer cell growth. All isolated compounds inhibited human topo II activity; the most potent were DBL and CA, which contain a catechol propanoid moiety. CA and DBL inhibited the activity of human topo I, whereas other compounds had no effect. No compound modulated the activities of 11 mammalian pol species or other DNA metabolic enzymes, including T7 RNA polymerase, mouse IMP dehydrogenase (type II), T4 polynucleotide kinase and bovine deoxyribonuclease I. CA and DBL markedly suppressed the proliferation of human colon HCT116 carcinoma cells with an LD50 of 70.0 and 49.4 µM, respectively, and halted the cell cycle in the G2/M phase. The suppressive effect of these compounds on cancer cell growth correlated with their ability to inhibit topo II. These results suggest that CA- and DBL-dependent decreases in cell proliferation are due to the inhibition of cellular topo II. The mechanism of action of these catechol propanoid compounds and the implication for their use as anticancer agents are discussed. AD - Laboratory of Food and Nutritional Sciences, Faculty of Nutrition, Kobe Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Akiha-ku, Niigata 956-8603, Japan Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan AU - Kuriyama,Isoko AU - Nakajima,Yuki AU - Nishida,Hiroshi AU - Konishi,Tetsuya AU - Takeuchi,Toshifumi AU - Sugawara,Fumio AU - Yoshida,Hiromi AU - Mizushina,Yoshiyuki DA - 2013/08/01 DO - 10.3892/mmr.2013.1547 EP - 542 IS - 2 JO - Mol Med Rep KW - low molecular weight polyphenolics Inonotus obliquus caffeic acid 3 4-dihydroxybenzalacetone DNA topoisomerase enzyme inhibitor cytotoxicity cell cycle arrest anticancer agents PY - 2013 SN - 1791-2997 1791-3004 SP - 535 ST - Inhibitory effects of low molecular weight polyphenolics from Inonotus obliquus on human DNA topoisomerase activity and cancer cell proliferation T2 - Molecular Medicine Reports TI - Inhibitory effects of low molecular weight polyphenolics from Inonotus obliquus on human DNA topoisomerase activity and cancer cell proliferation UR - https://doi.org/10.3892/mmr.2013.1547 VL - 8 ER -