Trans-resveratrol boronic acid exhibits enhanced anti-proliferative activity on estrogen-dependent MCF-7 breast cancer cells

Cancer Biol Ther. 2012 Aug;13(10):925-34. doi: 10.4161/cbt.20845. Epub 2012 Aug 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Boronic Acids / chemistry
  • Boronic Acids / pharmacology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm
  • Estrogens / metabolism*
  • Estrogens / pharmacology
  • Female
  • Humans
  • MCF-7 Cells
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Boronic Acids
  • Cell Cycle Proteins
  • Estrogens
  • Stilbenes
  • resveratrol boronic acid