title: Effects of tamoxifen versus raloxifene on retinal capillary endothelial cell proliferation.
abstract: OBJECTIVE
  Endothelial cell proliferation in angiogenesis is active in conditions such as cancers and diabetic retinopathy. Tamoxifen (T) and raloxifene (R) have been compared in numerous studies as a prophylaxis for breast cancer, and T is used to treat breast cancer. T, unlike R, has been linked to an increase in uterine cancers, thrombo-embolic events, and cataract. The purpose of our study was to evaluate the efficacies of T and R in reducing estrogen-induced retinal capillary endothelial cell proliferation.
  
  
  METHODS
  Rhesus monkey retinal capillary endothelial cells (ATCC RF/6A) were used to assay cell proliferation when treated with 0.0, 0.1, 1.0, and 10.0 nM 17 β estradiol (E2) for 24 and 48 h. Viable cells were counted using a Neubauer hemocytometer with a trypan blue exclusion method to determine the number of viable cells. Cell counts were also performed using 1.0 nM E2 with 0.01, 0.1, 1.0, and 10.0 nM concentrations of either T or R. Cell medium, collected at 24 h, was evaluated for vascular endothelial growth factor and pigment epithelium-derived factor.
  
  
  RESULTS
  Viable cells were significantly greater in cultures treated with 1.0 or 10.0 nM E2, compared to cells treated with 0.0 or 0.1 nM E2 both at 24 and 48 h. Viable cell counts were reduced significantly in cultures treated with 0.1, 1.0, or 10.0 nM T or R in addition to the 1.0 nM E2. Cell counts were not significantly different when comparing equal concentrations of T and R, that is, 1.0 nM E2+1 nM T or R. Vascular endothelial growth factor and pigment epithelium-derived factor protein/10,000 cells was reduced by 1.0 nM E2, but returned to higher levels with the introduction of T and R to growth media.
  
  
  CONCLUSIONS
  T and R showed similar potency in inhibiting estrogen-induced retinal capillary endothelial cell proliferation. Considering drug safety profiles, our results, when extended to animals and humans, suggest that R is preferable to T in treating angiogenic retinal diseases. Further studies on the signaling mechanism of estrogen-induced endothelial cell proliferation may lead to new treatment strategies in the treatment of ocular angiogenic diseases.
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
authors.forename: Jeffery G
authors.initials: JG
authors.lastname: Grigsby
authors.forename: Kalpana
authors.initials: K
authors.lastname: Parvathaneni
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Almanza
authors.forename: Angelica M
authors.initials: AM
authors.lastname: Botello
authors.forename: Albert A
authors.initials: AA
authors.lastname: Mondragon
authors.forename: Donald M
authors.initials: DM
authors.lastname: Allen
authors.forename: Andrew T C
authors.initials: AT
authors.lastname: Tsin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005136:Eye Proteins / Q000378:metabolism; D008253:Macaca mulatta; D009414:Nerve Growth Factors / Q000378:metabolism; D009994:Osmolar Concentration; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D015861:Retinal Neovascularization / Q000188:drug therapy; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D015843:Serpins / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D004958:Estradiol; D004965:Estrogen Antagonists; D004967:Estrogens; D005136:Eye Proteins; D009414:Nerve Growth Factors; D020849:Raloxifene Hydrochloride; D020845:Selective Estrogen Receptor Modulators; D015843:Serpins; D013629:Tamoxifen; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor