Solamargine induces apoptosis and enhances susceptibility to trastuzumab and epirubicin in breast cancer cells with low or high expression levels of HER2eu

摘要

Trastuzumab is used for breast cancer patients with high expression levels of HER2 (human epidermal growth factor receptor 2)eu; however, it has no effect on cancers with low levels of HER2eu. 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 HER2eu expression by SM was investigated. SM significantly up-regulates HER2eu expression in breast cancer cells with low and high expression levels of HER2eu, and synergistically enhanced the effect of trastuzumab in inhibiting cell proliferation. Additionally, HER2eu and TOP2A [TopoII (topoisomerase II) alpha] genes share the same amplicon on an identical chromosome. Notably, SM co-regulates HER2eu and TopoII alpha expression markedly, and enhances TopoII inhibitor-EPI (epirubicin)-induced cytotoxicity to breast cancer cells.