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

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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.

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Abbreviations

5-Fu:

5-fluorouracil

CDDP:

cisplatin

CI:

combination index

DMSO:

dimethyl sulfoxide

EPI:

epirubicin

MTS:

3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

MTX:

methotrexate

PBS:

phosphate-buffered saline

PMS:

phenazine methosulfate

SM:

solamargine

topoII:

topoisomerase II

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    L. Y. Shiu & K. W. Kuo

  2. Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Chia Nan, Taiwan

    C. H. Liang

  3. Department of Surgery, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Y. S. Huang

  4. Department of Dermatology, National Cheng Kung University, Tainan, Taiwan

    H. M. Sheu

  5. Research Center of Herbal Medicines, G&E Herbal Biotechnology, No. 26, Lane 31, Sec. 1, Huan Dong Rd., Tainan Science Park, SinShih, Tainan County, 74146, Taiwan

    K. W. Kuo

Authors
  1. L. Y. Shiu
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  2. C. H. Liang
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  3. Y. S. Huang
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  4. H. M. Sheu
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  5. K. W. Kuo
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Correspondence to K. W. Kuo.

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Shiu, L.Y., Liang, C.H., Huang, Y.S. et al. Downregulation of HER2/neu receptor by solamargine enhances anticancer drug-mediated cytotoxicity in breast cancer cells with high-expressing HER2/neu. Cell Biol Toxicol 24, 1–10 (2008). https://doi.org/10.1007/s10565-007-9010-5

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  • DOI: https://doi.org/10.1007/s10565-007-9010-5

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