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Abstract
BackgroundThe 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.ResultsBPH 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.ConclusionsThe results indicate that IAPs may represent interesting targets for drug therapy of BPH.
Highlights
The apoptosis machinery is a promising target against benign prostatic hyperplasia (BPH)
In order to better understand the molecular mechanism(s) of the triple therapeutic association Serenoa Repens (SeR)-Se-Ly on apoptosis, we studied the effects of SeR, Se and Ly, alone or in association, on the expression of four Inhibitors of apoptosis proteins (IAPs), cIAP-1, Cellular IAP-1 and IAP-2 (cIAP-2), neuronal apoptosis inhibitory protein (NAIP) and survivin in rats with experimental testosteronedependent BPH
After 1 week of stabilization, animals were randomly assigned to 6 groups: Sham administered with vehicle (100 μl corn oil subcutaneously), BPH receiving testosterone propionate (3 mg/kg/sc diluted in corn oil in a volume of 100 μl), BPH + SeR injected with SeR (25 mg/kg/sc in corn oil), BPH + Ly injected with Ly (1 mg/kg/sc, in corn oil), BPH + Se injected with Se (3 mg/kg/sc, in corn oil) and BPH + Ly-Se-SeR administered with the combination of Ly-Se-SeR for 14 days [14,15]
Summary
The apoptosis machinery is a promising target against benign prostatic hyperplasia (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. 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. Benign prostatic hyperplasia (BPH) is a common cause of bothersome lower urinary tract symptoms (LUTS). BPH results from smooth muscle and epithelial proliferation primarily within the prostatic transition zone that can produce LUTS [6,7,8,9]. As a consequence, targeting apoptosis may represent a rational therapeutic strategy in the treatment of BPH
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