title: In vivo and in vitro demonstration of herb-drug interference in human breast cancer cells treated with tamoxifen and trastuzumab.
abstract: OBJECTIVE
  In recent trends, patients with breast cancer seek integrative medical treatment when receiving either hormonal (tamoxifen [Tam]) or target (trastuzumab) therapy. Our previous in vitro studies demonstrated that the Chinese medicine Si-Wu-Tang (SWT) stimulates MCF-7 cell growth via activation of estrogen receptor α and human epidermal growth factor receptor 2 (HER2) signaling. The present study demonstrates herb-drug interference with cell proliferation in tumor-bearing mice treated with SWT and Tam in vivo and with proliferation capacity in breast cancer cells treated with SWT and trastuzumab in vitro.
  
  
  METHODS
  To assess in vivo SWT + Tam interference, we randomly separated female MCF-7-implanted athymic nude mice into five groups, namely, vehicle (n = 11), estradiol (n = 8), SWT (n = 8), Tam (n = 11), and SWT + Tam (n = 8). All mice were killed after 21 days of treatment. Body weight, uterine weight, tumor volume, and tumor weight were measured. To assess in vitro SWT-trastuzumab interference, we cotreated BT-474 and SK-BR-3 breast cancer cells with SWT and trastuzumab. This was followed by (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays and cell cycle analysis to measure cell proliferation and by Western blot analysis to analyze protein expression in growth-related signal pathways.
  
  
  RESULTS
  SWT reversed Tam-induced antiproliferative effects on tumor weight and tumor volume and increased estrogen receptor α and N-cadherin expression in the SWT + Tam-treated group compared with the Tam-treated group. Furthermore, SWT reversed trastuzumab-induced antiproliferative activity in HER2 cell lines (SK-BR-3 and BT-474) through increased phosphorylation of the cell cycle regulatory protein p27(Kip1) and possibly of the antiapoptosis protein P38.
  
  
  CONCLUSIONS
  Based on the in vivo and in vitro demonstration of herb-drug interference in breast cancer cells, we conclude that physicians should pay more attention to such interference when treating patients with receptor-positive (estrogen receptor-positive, progesterone receptor-positive, or HER2) breast cancers.
authors: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors: Jiun-Liang
authors: JL
authors: Chen
authors: Jir-You
authors: JY
authors: Wang
authors: Yi-Fang
authors: YF
authors: Tsai
authors: Yi-Hsien
authors: YH
authors: Lin
authors: Ling-Ming
authors: LM
authors: Tseng
authors: Wen-Chi
authors: WC
authors: Chang
authors: Kuan-Liang
authors: KL
authors: King
authors: Wei-Shone
authors: WS
authors: Chen
authors: Jen-Hwey
authors: JH
authors: Chiu
authors: Yi-Ming
authors: YM
authors: Shyr
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D015820:Cadherins / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010766:Phosphorylation / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D015820:Cadherins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004365:Drugs, Chinese Herbal; D004958:Estradiol; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D000068878:Trastuzumab; C403258:si-wu-tang