title: Fenretinide: A Potential Treatment for Endometriosis.
abstract: Fenretinide is a synthetic retinoid analogue that promotes apoptosis but has decreased toxicity when compared to other retinoids. We have previously shown that retinoic acid (RA) production in endometriotic tissue is decreased, resulting in reduced estrogen metabolism and apoptotic resistance. We hypothesize fenretinide may induce apoptosis in endometriotic cells and tissues, thereby reducing disease burden.
  
  
  
  Primary endometriotic stromal cells were collected, isolated, cultured, and treated with fenretinide in doses from 0 to 20 µmol/L. Cell count, viability, and immunoblots were performed to examine apoptosis. Quantitative reverse transcription-polymerase chain reaction from endometriotic cells treated with fenretinide was used to examine expression of genes involved in RA signaling including stimulated by RA 6 (STRA6), cellular RA binding protein 2 (CRABP2), and fatty acid binding protein 5 (FABP5). Endometriotic tissue was xenografted subcutaneously into the flanks of mice which were treated with fenretinide for 2 weeks, after which the mice were killed and lesion volumes calculated. Statistical analysis was performed using t test and analysis of variance.
  
  
  
  Treatment with fenretinide significantly decreased total cell count (doses 5-20 µL) and viability (doses 10-20 µmol/L). Fenretinide increased protein levels of the apoptotic marker poly (ADP ribose) polymerase (starting at 10 µmol/L) and decreased proliferation marker proliferating cell nuclear antigen (10 µmol/L, starting at 8-day treatment). Examination of genes involved in retinoid uptake and action showed that treatment induced STRA6 expression while expression of CRABP2 and FABP5 remained unchanged. Fenretinide also significantly decreased the endometriotic lesion xenograft volume.
  
  
  
  Fenretinide increases STRA6 expression thereby potentially reversing the pathological loss of retinoid availability. Treatment with this compound induces apoptosis. In vivo treatments decrease lesion volume. Targeting the RA signaling pathway may be a promising novel treatment for women with endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA m-pavone@northwestern.edu.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Saurabh S
authors.initials: SS
authors.lastname: Malpani
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Dyson
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: J Julie
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; C519685:STRA6 protein, human; D017313:Fenretinide; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: STRA6; apoptosis; endometriosis; fenretinide; retinoic acid; retinoid; retinol