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International Journal of Pharmacology

Year: 2005 | Volume: 1 | Issue: 2 | Page No.: 138-151
DOI: 10.3923/ijp.2005.138.151
Novel Topoisomerase I and II Inhibitors, Parameritannins A-2 and A-3, are Selective Human Cancer Cytotoxins
Chikako Nakai, Kohei Kamiya, Toshiko Satake, Isoko Kuriyama, Hiroshi Iijima, Hiroshi Ikawa, Hiromi Yoshida and Yoshiyuki Mizushina

Abstract: Present study, isolated the parameritannins A-2 and A-3, new A-type tetrameric proanthocyanidins, from the bark of Parameria laerigata Moldenke and showed that they inhibited eukaryotic topos I, II or both activities in vitro. Although they are structurally isomeric compounds, their inhibitory effects against topos were different. Parameritannin A-2 only inhibited topo II activity with IC50 value of 0.5 μM, while parameritannin A-3 inhibited both topos I and II activities with IC50 values of 50 and 0.5 μM, respectively. The inhibitory actions of parameritannin A-3 against topos I and II were also different. Preincubation analysis suggests that parameritannin A-3 binds both topo I and substrate DNA and it has high binding affinity to DNA rather than topo I. Inhibitory activity against topo II was same for either pretreatment with enzyme or DNA. In addition, only parameritannin A-3 induced apoptosis although both parameritannins A-2 and A-3 arrested the cell cycle at G2/M phase. This is the first report that parameritannins act as topo inhibitors and present results further support its therapeutic potential as a leading anti-cancer compound that poisons topos.

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Chikako Nakai, Kohei Kamiya, Toshiko Satake, Isoko Kuriyama, Hiroshi Iijima, Hiroshi Ikawa, Hiromi Yoshida and Yoshiyuki Mizushina, 2005. Novel Topoisomerase I and II Inhibitors, Parameritannins A-2 and A-3, are Selective Human Cancer Cytotoxins. International Journal of Pharmacology, 1: 138-151.

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