Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells.
10.3858/emm.2009.41.3.018
- Author:
Young Bin HONG
1
;
Hyo Jin KANG
;
Hee Jeong KIM
;
Eliot M ROSEN
;
Sivanesan DAKSHANAMURTHY
;
Riccardo RONDANIN
;
Riccardo BARUCHELLO
;
Giuseppina GRISOLIA
;
Simoni DANIELE
;
Insoo BAE
Author Information
1. Department of Oncology, Georgetown University, 3970 Reservoir Road, NW Washington DC, 20057-1469, USA. ib42@georgetown.edu
- Publication Type:Original Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
- Keywords:
antineoplastic agents, phytogenic;
breast neoplasms;
cell cycle;
cis-3,4',5-trimethoxy-3'-hydroxystilbene;
pancreatic neoplasms;
resveratrol;
tubulin
- MeSH:
Antineoplastic Agents/*pharmacology;
Binding Sites;
Breast Neoplasms;
Cell Cycle/drug effects;
Cell Line, Tumor;
Cell Proliferation/*drug effects;
Colchicine/chemistry/pharmacology;
Cyclin B/metabolism;
G2 Phase/drug effects;
Humans;
Microtubules/drug effects/metabolism;
Models, Molecular;
Pancreatic Neoplasms;
Protein-Serine-Threonine Kinases/metabolism;
Stilbenes/*pharmacology;
Tubulin/metabolism
- From:Experimental & Molecular Medicine
2009;41(3):151-160
- CountryRepublic of Korea
- Language:English
-
Abstract:
Resveratrol has been reported to possess cancer preventive properties. In this study, we analyzed anti-tumor activity of a newly synthesized resveratrol analog, cis-3,4',5-trimethoxy-3'-hydroxystilbene (hereafter called 11b) towards breast and pancreatic cancer cell lines. 11b treatments reduced the proliferation of human pancreatic and breast cancer cells, arrested cells in the G2/M phase, and increased the percentage of cells in the subG1/G0 fraction. The 11b treatments also increased the total levels of mitotic checkpoint proteins such as BubR1, Aurora B, Cyclin B, and phosphorylated histone H3. Mechanistically, 11b blocks microtubule polymerization in vitro and it disturbed microtubule networks in both pancreatic and breast cancer cell lines. Computational modeling of the 11b-tubulin interaction indicates that the dimethoxyphenyl group of 11b can bind to the colchicine binding site of tubulin. Our studies show that the 11b treatment effects occur at lower concentrations than similar effects associated with resveratrol treatments and that microtubules may be the primary target for the observed effects of 11b. These studies suggest that 11b should be further examined as a potentially potent clinical chemotherapeutic agent for treating pancreatic and breast cancer patients.
