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 Solanum 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) α] genes share the same amplicon on an identical chromosome. Notably, SM co-regulates HER2/neu and TopoIIα expression markedly, and enhances TopoII inhibitor–EPI (epirubicin)-induced cytotoxicity to breast cancer cells.
Solamargine induces apoptosis and enhances susceptibility to trastuzumab and epirubicin in breast cancer cells with low or high expression levels of HER2/neu
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Li Yen Shiu, Chia Hua Liang, Li Ching Chang, Hamm Ming Sheu, Eing Mei Tsai, Kou Wha Kuo; Solamargine induces apoptosis and enhances susceptibility to trastuzumab and epirubicin in breast cancer cells with low or high expression levels of HER2/neu. Biosci Rep 1 February 2009; 29 (1): 35–45. doi: https://doi.org/10.1042/BSR20080028
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