Downregulation of HER2/neu receptor by solamargine enhances anticancer drug-mediated cytotoxicity in breast cancer cells with high-expressing HER2/neu

Cell Biol Toxicol. 2008 Jan;24(1):1-10. doi: 10.1007/s10565-007-9010-5. Epub 2007 Sep 19.

Abstract

Overexpression of HER2/neu is associated with drug resistance and poor outcome in breast cancer. Solamargine (SM), a glycoalkaloid purified from the herb Solanum incanum, exhibits HER2/neu gene modulation of HER2/neu high-expressing human breast cancer cell line ZR-75-1. SM downregulation of HER2/neu gene expression was determined by RT-PCR and Southern hybridization. Additionally, the membrane-bound HER2/neu receptor in highly HER2/neu-expressing breast cancer cells was determined by radioimmunoassay, immunocytochemistry, fluorescent immunocytochemistry, and flow cytometry. SM significantly decreased the number of HER2/neu receptors on the cell membrane. Methotrexate (MTX), 5-florouracil (5-Fu), and cisplatin (CDDP) are commonly used for breast carcinoma treatment in clinics; however, patients with HER2/neu overexpression exhibit resistance to these anticancer drugs. Notably, combination of MTX, 5-Fu, and CDDP with SM individually increased the susceptibility of breast cancer cells to these chemotherapeutic agents. Experimental results indicated that downregulation of HER2/neu by SM might be an effective strategy for enhancing drug susceptibility of breast cancer cells expressing high levels of HER2/neu.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Southern
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects*
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Radioimmunoassay
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Solanaceous Alkaloids / pharmacology*

Substances

  • Antineoplastic Agents
  • Solanaceous Alkaloids
  • beta-solamarine
  • Receptor, ErbB-2