Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonsmall-cell lung cancer (NSCLC) is not generally a chemosensitive tumor, and the mechanism of resistance to the relevant anticancer drugs has not been fully elucidated. Solamargine (SM), the major steroidal glycoalkaloids extracted from the Chinese herb Solanum, inhibits the growth of human tumor cells. We have previously demonstrated that SM regulates tumor necrosis factor receptors (TNFRs)- and mitochondria-mediated pathways and sensitizes NSCLC cells to initiate apoptosis. Interestingly, this investigation reveals that SM up-regulated Fas expression and down-regulated the expression of HER2, whose overexpression is associated with resistance to drugs, and promotes chemotherapy-induced apoptosis in NSCLC A549 and H441 cells. After treatment with SM, the expression of HER2 mRNA was correlated with the expression of topoisomerase IIalpha (TOP2A) mRNA. The combinatory use of low concentrations of SM with low-toxic topoisomerase II inhibitor epirubicin accelerated apoptotic cell death. Therefore, the downregulation of the HER2 and TOP2A expression by SM with epirubicin may partially explain the SM and epirubicin cytotoxicity synergy effect in NSCLC. Results of this study suggest that SM induces Fas and TNFR-induced NSCLC cell apoptosis and reduces HER2 expression. These findings provide the synergistic therapeutic interaction between SM and epirubicin, suggesting that such combinations may be effectively exploited in future human cancer clinical trials.
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PMID:Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. 1763 97

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.
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PMID:Downregulation of HER2/neu receptor by solamargine enhances anticancer drug-mediated cytotoxicity in breast cancer cells with high-expressing HER2/neu. 1788 15