A novel antitumor activity of deguelin targeting the insulin-like growth factor (IGF) receptor pathway via up-regulation of IGF-binding protein-3 expression in breast cancer

Cancer Lett. 2013 May 10;332(1):102-9. doi: 10.1016/j.canlet.2013.01.022. Epub 2013 Jan 21.

Abstract

In this study, we investigated the antitumor effects of deguelin in several human breast cancer cells in vitro and in vivo. Deguelin inhibited cell viability and the anchorage-dependent and anchorage-independent colony formation of triple-negative (MDA-MB-231 and MDA-MB-468) and triple-positive (MCF-7) breast cancer cells, and it significantly reduced the growth of MCF-7 cell xenograft tumors. The induction of apoptosis, inhibition of insulin-like growth factor-1 receptor (IGF-1R) signaling activation, and up-regulation of IGF-binding protein-3 (IGFBP-3) expression may be associated with deguelin-mediated antitumor effects. Our findings suggest a potential therapeutic use for deguelin in patients with triple-negative breast cancer and for those with breast cancers who are sensitive to endocrine- and HER2-targeted therapies.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / drug effects*
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • RNA Interference
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Receptors, Somatomedin / metabolism*
  • Rotenone / analogs & derivatives*
  • Rotenone / pharmacology
  • Signal Transduction / drug effects*
  • Survivin
  • Time Factors
  • Transfection
  • Tumor Burden / drug effects
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • IGFBP3 protein, human
  • Inhibitor of Apoptosis Proteins
  • Insulin-Like Growth Factor Binding Protein 3
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptors, Somatomedin
  • Survivin
  • Rotenone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • deguelin