title: A retrospective in vitro study of the impact of anti-diabetics and cardioselective pharmaceuticals on breast cancer.
abstract: BACKGROUND
  In a retrospective controlled study, a tumor-protective effect, regarding breast cancer, was determined for the medicines metformin and glitazone (anti-diabetics), bisoprolol, and propranolol (cardioselective β1 adrenoceptor antagonists). Our main goal was to provide evidence, showing the tumor-protective effects of beta-blockers and of antidiabetics via investigations in vitro.
  
  
  METHODS
  Four different medicines were tested in cell cultures: Propranolol: 2.4 mg/ml and 0.3 mg/ml; bisoprolol: 0.1 mg/ml and 0.05 mg/ml; metformin: 7.5 mg/ml, 2.5 mg/ml, and 0.15 mg/ml; and glitazone: 2.5 mg/ml, 0.15 mg/ml, and 0.05 mg/ml. The human breast cancer cell lines MCF7 and BT20 (estrogen receptor-positive and -negative; ATCC; cell density: 5×10(5) cells/ml) were used. Both cell lines were cultured under sterile conditions in incubators at 37°C, with a humidified atmosphere of 5% CO(2). The influences of the drugs were determined through cytotoxicity and proliferation assays and performance of a hydrogen peroxide assay. Morphological observations (light microscopy) and metabolic investigations (pH value, glucose) were also performed.
  
  
  RESULTS
  The application of the beta-blocker propranolol resulted in highly cytotoxic effects (>90%) in both cell lines. In contrast, bisoprolol did not have any effects, neither in cytotoxicity tests nor in cell proliferation assays. The anti-diabetic metformin had a higher cytotoxic influence on the BT20 than did on the MCF7 cell line. The cell proliferation of BT20 was significantly inhibited after the addition of 2.5 mg/ml metformin and of 2.5 mg/ml glitazone. The application of glitazone also resulted in an increase of hydrogen peroxide and a decrease of the pH value.
  
  
  CONCLUSIONS
  The strongest cytotoxic effect was observed with propranolol suggesting that, in clinical practice, this pharmaceutical can be used in patients with breast cancer who have hypertension. A specific clinical recommendation for anti-diabetics is not yet possible.
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Südring 81, D-18059 Rostock, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Szewczyk
authors.forename: C
authors.initials: C
authors.lastname: Richter
authors.forename: V
authors.initials: V
authors.lastname: Briese
authors.forename: D-U
authors.initials: DU
authors.lastname: Richter
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D017298:Bisoprolol / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology; D018384:Oxidative Stress; D011433:Propranolol / Q000494:pharmacology; D012189:Retrospective Studies; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; D011433:Propranolol; D006861:Hydrogen Peroxide; D017298:Bisoprolol