Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells.
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.
Hong
Young Bin
YB
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW Washington DC, 20057-1469, USA.
Kang
Hyo Jin
HJ
Kim
Hee Jeong
HJ
Rosen
Eliot M
EM
Dakshanamurthy
Sivanesan
S
Rondanin
Riccardo
R
Baruchello
Riccardo
R
Grisolia
Giuseppina
G
Daniele
Simoni
S
Bae
Insoo
I
D000970:Antineoplastic Agents / Q000494:pharmacology*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001665:Binding Sites; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003078:Colchicine / Q000737:chemistry / Q000494:pharmacology; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D010190:Pancreatic Neoplasms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D013267:Stilbenes; D014404:Tubulin; C529078:cis-3,4',5-trimethoxy-3'-hydroxystilbene; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D000077185:Resveratrol; D003078:Colchicine