Authors: Venkata Mahidhar Yenugonda, Yali Kong, Tushar B. Deb, Yonghong Yang, Rebecca B. Riggins and Milton L. Brown

Venkata Mahidhar Yenugonda

Drug Discovery Program; Georgetown University Medical Center; Washington, DC USA; Department of Oncology and Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA
These authors contributed equally to this work.

Yali Kong

Drug Discovery Program; Georgetown University Medical Center; Washington, DC USA; Department of Oncology and Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA
These authors contributed equally to this work.

Tushar B. Deb

Department of Oncology and Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA

Yonghong Yang

Drug Discovery Program; Georgetown University Medical Center; Washington, DC USA; Department of Oncology and Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA

Rebecca B. Riggins

Department of Oncology and Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA

Milton L. Brown

Corresponding author: mb544@georgetown.edu
Drug Discovery Program; Georgetown University Medical Center; Washington, DC USA; Department of Oncology and Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA

Abstract:
Resveratrol (RSV), a natural compound present in the skin and seeds of red grapes, is considered a phytoestrogen and has structural similarity to the synthetic estrogen diethylstilbestrol. RSV inhibits tumor cell growth in estrogen receptor-positive (ER+) and negative (ER-) breast cancer cell lines resulting in cell specific regulation of the G₁/S and G₂/M stages of the cell cycle. However apoptotic cell death was only observed in ER+ MCF-7 cells. In this study, we designed and synthesized boronic acid derivative of RSV and evaluated their biological effects on ER+ MCF-7 breast cancer cells. The trans-4 analog inhibited the growth of MCF-7 cells and is not a substrate for p-glycoprotein. The trans-4 analog induces G₁ cell cycle arrest, which coincides with marked inhibition of G₁ cell cycle proteins and a greater pro-apoptotic effect. Finally, the trans-4 analog had no effect on the estrogen-stimulated growth of MCF-7 cells. Our results demonstrate that the trans-4 analog inhibits MCF-7 breast cancer cells by a different mechanism of action than that of RSV (S-phase arrest), and provides a new class of novel boronic acids of RSV that inhibit breast cancer cell growth.

Received: March 15, 2012; Accepted: May 22, 2012

Preview: