title: Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice.
abstract: BACKGROUND
  Resveratrol, a polyphenol from grapes and red wine has many health beneficial effects, including protection against cardiovascular and neurodegenerative diseases and cancer. However, our group and others have provided evidence for a dual cancer promoting or inhibitory role for resveratrol in breast cancer, dependent on estrogenic or antiestrogenic activities. Moreover, much of the inhibitory effects of resveratrol have been reported from studies with high non-physiological concentrations.
  
  
  METHODS
  We investigated the effects of a range of concentrations (0.5, 5, 50 mg/kg body weight) of resveratrol on mammary tumor development post-initiation, using immunocompromised mice.
  
  
  RESULTS
  Our findings suggest promotion of mammary tumor growth and metastasis by resveratrol at all concentrations tested in tumors derived from the low metastatic estrogen receptor (ER)α(-), ERβ(+) MDA-MB-231 and the highly metastatic ER(-) MDA-MB-435 cancer cell lines. Additionally, the activity of the migration/invasion regulator Rac, which we have previously shown to be regulated by resveratrol in vitro, was measured in tumors from resveratrol treated mice. Our results show a significant induction of tumoral Rac activity and a trend in increased expression of the Rac downstream effector PAK1 and other tumor promoting molecules following resveratrol treatment.
  
  
  CONCLUSIONS
  Taken together, our findings implicate low concentrations of resveratrol in potential promotion of breast cancer. Therefore, this study illuminates the importance of further delineating resveratrol's concentration dependent effects, particularly in breast cancer, before it can be tested in the clinic or used as a dietary supplement for breast cancer patients.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, USA.
authors.forename: Linette
authors.initials: L
authors.lastname: Castillo-Pichardo
authors.forename: Luis A
authors.initials: LA
authors.lastname: Cubano
authors.forename: Suranganie
authors.initials: S
authors.lastname: Dharmawardhane
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D051379:Mice; D008812:Mice, Hairless; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010936:Plant Extracts / Q000009:adverse effects*; D059808:Polyphenols / Q000009:adverse effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000009:adverse effects*; D027843:Vitis / Q000737:chemistry*; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010936:Plant Extracts; D059808:Polyphenols; D011960:Receptors, Estrogen; D013267:Stilbenes; C515905:Pak1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D000077185:Resveratrol