Catalytic inhibition of eukaryotic topoisomerases I and II by flavonol glycosides extracted from Vicia faba and Lotus edulis.
Topoisomerases are essential enzymes involved in all processes of DNA metabolism, and their inhibitors have been identified as potential anticancer agents. The present study examined the effect of nine polyphenolic compounds derived from parts of two unique varieties of the Leguminosae, Vicia faba and Lotus edulis, on the activity of eukaryotic topoisomerases. We identified polyphenolic compounds that act as catalytic inhibitors of wheat germ topoisomerase I (IC50: 120-350 μM), human topoisomerase I (IC50: 110-260 μM), and human topoisomerase II (IC50: 240-600 μM) activities. Some compounds inhibited all enzymatic activities to a similar extent, while others exhibited specificity toward individual enzymes. The strongest catalytic inhibitor of all the examined enzymes was a kaempherol glycoside with an acetyl group linked to a sugar moiety. In addition, this compound inhibited the growth of human cancer cell lines MCF7, HeLa, and HepG2. The inhibition of topoisomerase I and II activities observed by the specific compounds possibly implies a role as potential agents in the prevention and therapy of cancer.
Department of Biochemistry and Biotechnology, University of Thessaly, Greece.
Maria
M
Tselepi
Evaggelia
E
Papachristou
Aikaterini
A
Emmanouilidi
Apostolos
A
Angelis
Nektarios
N
Aligiannis
Alexios-Leandros
AL
Skaltsounis
Demetrios
D
Kouretas
Kalliopi
K
Liadaki
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D044948:Flavonols / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006115:Greece; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D000070116:Lotus / Q000737:chemistry*; D015394:Molecular Structure; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D031307:Vicia faba / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D044948:Flavonols; D006027:Glycosides; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors