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.

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.

• Authors: Young-Ah Suh, Jai-Hyun Kim, Myung A Sung, Hye-Jin Boo, Hye Jeong Yun, Sun-Hye Lee, Hyo-Jong Lee, Hye-Young Min, Young-Ger Suh, Kyu-Won Kim, Ho-Young Lee
• Journal: Cancer letters (Cancer Lett) Vol. 332 Issue 1 Pg. 102-9 (May 10 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23348700 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (drug therapy, genetics, metabolism, 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, genetics, 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, pharmacology)
• Signal Transduction (drug effects)
• Survivin
• Time Factors
• Transfection
• Tumor Burden (drug effects)
• Up-Regulation
• Xenograft Model Antitumor Assays