Stilbenes are a group of natural compounds with many biological activities. Two highly potent stilbenes, cis-3,4',5-trimethoxy-3'-aminostilbene (stilbene 5c) and cis-3,4',5-trimethoxy-3'-hydroxystilbene (stilbene 6c) induce G(2)/M cell-cycle arrest and leukemic cell death in nanomolarity range without affecting normal bone marrow progenitor cells. The mechanism of stilbenes is mediated by interfering with microtubule polymerization through the colchicine-binding site. Docking of the stilbenes into tubulin structure confirms that stilbenes fit into the colchicine-binding pocket. Animal studies show that stilbenes are well tolerated in mice and are capable of inducing more than 50\% leukemic cell death by a single dose injection. A 5-day treatment with low-dose stilbenes suppresses tumor growth in mice with established tumor xenografts. No major organ damage was detected by histological section. Our results indicate that stilbene 5c is a microtubule-interfering agent and can be potentially useful in leukemic therapy.

Stilbene derivatives that are colchicine site microtubule inhibitors have antileukemic activity and minimal systemic toxicity.

SIMONI, Daniele;
2008

Abstract

Stilbenes are a group of natural compounds with many biological activities. Two highly potent stilbenes, cis-3,4',5-trimethoxy-3'-aminostilbene (stilbene 5c) and cis-3,4',5-trimethoxy-3'-hydroxystilbene (stilbene 6c) induce G(2)/M cell-cycle arrest and leukemic cell death in nanomolarity range without affecting normal bone marrow progenitor cells. The mechanism of stilbenes is mediated by interfering with microtubule polymerization through the colchicine-binding site. Docking of the stilbenes into tubulin structure confirms that stilbenes fit into the colchicine-binding pocket. Animal studies show that stilbenes are well tolerated in mice and are capable of inducing more than 50\% leukemic cell death by a single dose injection. A 5-day treatment with low-dose stilbenes suppresses tumor growth in mice with established tumor xenografts. No major organ damage was detected by histological section. Our results indicate that stilbene 5c is a microtubule-interfering agent and can be potentially useful in leukemic therapy.
Thai M., Cao; David, Durrant; Ashutosh, Tripathi; Jihua, Liu; Schickwann, Tsai; Glen E., Kellogg; Simoni, Daniele; Ray M., Lee
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/520838
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