1: Int J Cancer. 2003 Nov 1;107(2):189-196. Related Articles, Links


Resveratrol analog (Z)-3,5,4'-trimethoxystilbene is a potent anti-mitotic drug
inhibiting tubulin polymerization.

Schneider Y, Chabert P, Stutzmann J, Coelho D, Fougerousse A, Gosse F, Launay
JF, Brouillard R, Raul F.

Laboratory of Nutritional Oncology, Inserm U392, IRCAD, Strasbourg, France.

Resveratrol (3,5,4'-trihydroxystilbene) a natural polyphenol present in
medicinal plants, grapes and wines, has potent chemopreventive properties on
intestinal carcinogenesis. A methylated derivative (Z-3,5,4'-trimethoxystilbene:
R3) was synthesized. R3 at 0.3 microM exerted a 80% growth inhibition of human
colon cancer Caco-2 cells and arrested growth completely at 0.4 microM (R3 was
100-fold more active than resveratrol). The cis conformation of R3 was also
100-fold more potent than the trans isomer. R3 (0.3 microM) caused cell cycle
arrest at the G2/M phase transition. The drug inhibited tubulin polymerization
in a dose-dependent manner (IC(50)= 4 microM), and it reduced also by 2-fold
ornithine decarboxylase and s-adenosylmethionine decarboxylase activities. This
caused the depletion of the polyamines, putrescine and spermidine, which are
growth factors for cancer cells. R3 inhibited partially colchicine binding to
its binding site on tubulin, indicating that R3 either partially overlaps with
colchicine binding or that R3 binds to a specific site of tubulin that is not
identical with the colchicine binding site modifying colchicine binding by
allosteric influences. The resveratrol derivative (Z)-3,5,4'-trimethoxystilbene
(R3) is an interesting anti-mitotic drug that exerts cytotoxic effects by
depleting the intracellular pool of polyamines and by altering microtubule
polymerization. Such a drug may be useful for the treatment of neoplastic
diseases. Copyright 2003 Wiley-Liss, Inc.

PMID: 12949793 [PubMed - as supplied by publisher]

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