title: Carnosic acid inhibits the growth of ER-negative human breast cancer cells and synergizes with curcumin.
abstract: BACKGROUND
  Studies indicate that extracts and purified components, including carnosic acid, from the herb rosemary display significant growth inhibitory activity on a variety of cancers.
  
  
  OBJECTIVE
  This paper examines the ability of rosemary/carnosic acid to inhibit the growth of human breast cancer cells and to synergize with curcumin.
  
  
  METHODS
  To do this, we treated human breast cancer cells with rosemary/carnosic acid and assessed effects on cell proliferation, cell cycle distribution, gene expression patterns, activity of the purified Na/K ATPase and combinations with curcumin.
  
  
  RESULTS
  Rosemary/carnosic acid potently inhibits proliferation of ER-negative human breast cancer cells and induces G1 cell cycle arrest. Further, carnosic acid is selective for MCF7 cells transfected for Her2, indicating that Her2 may function in its action. To reveal primary effects, we treated ER-negative breast cancer cells with carnosic acid for 6h. At a low dose, 5 μg/ml (15 μM), carnosic acid activated the expression of 3 genes, induced through the presence of antioxidant response elements, including genes involved in glutathione biosynthesis (CYP4F3, GCLC) and transport (SLC7A11). At a higher dose, 20 μg/ml, carnosic acid activated the expression of antioxidant (AKR1C2, TNXRD1, HMOX1) and apoptosis (GDF15, PHLDA1, DDIT3) genes and suppressed the expression of inhibitor of transcription (ID3) and cell cycle (CDKN2C) genes. Carnosic acid exhibits synergy with turmeric/curcumin. These compounds inhibited the activity of the purified Na-K-ATPase which may contribute to this synergy.
  
  
  CONCLUSIONS
  Rosemary/carnosic acid, alone or combined with curcumin, may be useful to prevent and treat ER-negative breast cancer.
authors: Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. lseinbond@gmail.com
authors: Linda Saxe
authors: LS
authors: Einbond
authors: Hsan-Au
authors: HA
authors: Wu
authors: Ryota
authors: R
authors: Kashiwazaki
authors: Kan
authors: K
authors: He
authors: Marc
authors: M
authors: Roller
authors: Tao
authors: T
authors: Su
authors: Xiaomei
authors: X
authors: Wang
authors: Sarah
authors: S
authors: Goldsberry
mesh_terms: D045784:Abietanes / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D027542:Rosmarinus / Q000737:chemistry*
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D003474:Curcumin; D005978:Glutathione; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D010936:Plant Extracts; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C075640:ID3 protein, human; C508053:ERBB2 protein, human; C018381:salvin