Exp Mol Med.  2009 Mar;41(3):151-160. 10.3858/emm.2009.41.3.018.

Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells

• Hong YB
• Kang HJ
• Kim HJ
• Rosen EM
• Dakshanamurthy S
• Rondanin R
• Baruchello R
• Grisolia G
• Daniele S
• Bae I

• KMID: 1123462
• DOI: http://doi.org/10.3858/emm.2009.41.3.018

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.

Keyword

antineoplastic agents, phytogenic; breast neoplasms; cell cycle; cis-3,4',5-trimethoxy-3'-hydroxystilbene; pancreatic neoplasms; resveratrol; tubulin

MeSH Terms

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