title: Vitamin D favorably alters the cancer promoting prostaglandin cascade.
abstract: BACKGROUND
  Preclinical studies suggest that 1,25-dihydroxyvitamin D [1,25(OH)2D] and celecoxib inhibit prostaglandins (PGs) associated with cancer through different mechanisms. We determined if there was synergy in their use.
  
  
  METHODS
  A total of 36 healthy women received daily for one month/menstrual cycle: placebo, 400 international units (IU) vitamin D-3, 2,000 IU vitamin D-3, or 2,000 IU vitamin D-3 plus 400 mg celecoxib. Serum and nipple aspirate fluid (NAF) were analyzed for PGE2 and transforming growth factor (TGF)β1 and -2; serum for 25(OH)D (total, -D-2, -D-3), plasma for celecoxib; and mammary duct RNA for cyclooxygenase (COX)2.
  
  
  RESULTS
  25(OH)D-3 increased (p<0.01) only in the groups receiving 2,000 IU vitamin D-3. PGE2 decreased in the breast (p=0.01) only after receiving 2,000 IU vitamin D-3; 2,000 IU vitamin D-3 alone was more effective in decreasing PGE2 than 2,000 IU vitamin D-3 plus celecoxib (p=0.018). COX2 expression decreased only in the breasts of women taking 2,000 IU vitamin D-3. Change in circulating 25(OH)D-3 correlated with change in TGFβ2 in the breast.
  
  
  CONCLUSIONS
  Vitamin D-3 reduces the PG cascade and increases TGFβ2 in a dose-dependent fashion. Adding celecoxib did not provide synergy.
authors.affiliation: 11937 U.S. Hwy 271, Tyler, TX, U.S.A. edward.sauter@uthct.edu.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qin
authors.forename: Claris
authors.initials: C
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Jensen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Holick
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
mesh_terms: D000328:Adult; D000068579:Celecoxib; D002762:Cholecalciferol / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D010919:Placebos; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D012313:RNA / Q000097:blood; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D010919:Placebos; D011448:Prostaglandin Antagonists; D011720:Pyrazoles; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D014807:Vitamin D; D002762:Cholecalciferol; D012313:RNA; C104450:25-hydroxyvitamin D; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone
keywords: Vitamin D; breast cancer prevention; prostaglandin inhibition