Journal
BIOSCIENCE REPORTS
Volume 29, Issue 1, Pages 35-45Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BSR20080028
Keywords
epirubicin (EPI); HER2/neu; solamargine (SM); topoisomerase II alpha (TopoII alpha); trastuzumab
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Funding
- National Science Council of Taiwan [NSC 97-2320-b-041-002-MY3]
- G&E Herbal Biotechnology
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Trastuzumab is used for breast cancer patients with high expression levels of HER2 (human epidermal growth factor receptor 2)/neu; however, it has no effect on cancers with low levels of HER2/neu. SM (solamargine), a major steroidal alkaloid glycoside purified from Solarium incanum, triggered apoptosis of breast cancer cells (MCF-7 and SK-BR-3 cells) and non-cancerous breast epithelial cells (HBL-100 cells) within 3 h. To extend the application of trastuzumab in breast cancer patients, the regulation of HER2/neu expression by SM was investigated. SM significantly up-regulates HER2/neu expression in breast cancer cells with low and high expression levels of HER2/neu, and synergistically enhanced the effect of trastuzumab in inhibiting cell proliferation. Additionally, HER2/neu and TOP2A [TopoII (topoisomerase II) alpha] genes share the same amplicon on an identical chromosome. Notably, SM co-regulates HER2/neu and TopoII alpha expression markedly, and enhances TopoII inhibitor-EPI (epirubicin)-induced cytotoxicity to breast cancer cells.
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