title: Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of serenoa repens, selenium and lycopene.
abstract: BACKGROUND
  The apoptosis machinery is a promising target against benign prostatic hyperplasia (BPH). Inhibitors of apoptosis proteins (IAPs) modulate apoptosis by direct inhibition of caspases. Serenoa Repens (SeR) may be combined with other natural compounds such as Lycopene (Ly) and Selenium (Se) to maximize its therapeutic activity in BPH. We investigated the effects of SeR, Se and Ly, alone or in association, on the expression of four IAPs, cIAP-1, cIAP-2, NAIP and survivin in rats with experimental testosterone-dependent BPH. Moreover, caspase-3, interleukin-6 (IL-6) and prostate specific membrane antigen (PSMA) have been evaluated.Rats were administered, daily, with testosterone propionate (3 mg/kg/sc) or its vehicle for 14 days. Testosterone injected animals (BPH) were randomized to receive vehicle, SeR (25 mg/kg/sc), Se (3 mg/kg/sc), Ly (1 mg/kg/sc) or the SeR-Se-Ly association for 14 days. Animals were sacrificed and prostate removed for analysis.
  
  
  RESULTS
  BPH animals treated with vehicle showed unchanged expression of cIAP-1 and cIAP-2 and increased expression of NAIP, survivin, caspase-3, IL-6 and PSMA levels when compared with sham animals. Immunofluorescence studies confirmed the enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization. SeR-Se-Ly association showed the highest efficacy in reawakening apoptosis; additionally, this therapeutic cocktail significantly reduced IL-6 and PSMA levels. The administration of SeR, Se and Ly significantly blunted prostate overweight and growth; moreover, the SeR-Se-Ly association was most effective in reducing prostate enlargement and growth by 43.3% in treated animals.
  
  
  CONCLUSIONS
  The results indicate that IAPs may represent interesting targets for drug therapy of BPH.
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Rinaldi
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pizzino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Salvatore
authors.initials: S
authors.lastname: Arena
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cimino
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.affiliation: Department of Urology, Polyclinic Hospital, University of Catania, Catania 95100, Italy. giorgioivan@virgilio.it.
authors.forename: Giorgio Ivan
authors.initials: GI
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Morgia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D002338:Carotenoids / Q000008:administration & dosage* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000008:administration & dosage*; D000077276:Lycopene; D008297:Male; D008517:Phytotherapy; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D028024:Serenoa / Q000737:chemistry
chemical_list: D051017:Apoptosis Regulatory Proteins; D051034:Inhibitor of Apoptosis Proteins; D002338:Carotenoids; D000077276:Lycopene