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