Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study

Abstract

Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated that Serenoa repens (Ser) with lycopene (Ly) and selenium (Se) reawakened apoptosis by reducing survivin and neuronal apoptosis inhibitory protein (NAIP) levels in rats. The aim of this study was to evaluate the effectiveness of Ser-Se-Ly association on survivin and NAIP expression in BPH patients. Ninety patients with lower urinary tract symptoms (LUTS) due to clinical BPH were included in this randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive placebo (Group BPH + placebo, n = 45) or Ser-Se-Ly association (Group BPH + Ser-Se-Ly; n = 45) for 3 months. At time 0, all patients underwent prostatic biopsies. After 3 months of treatment, they underwent prostatic re-biopsy and specimens were collected for molecular, morphological, and immunohistochemical analysis. After 3 months, survivin and NAIP were significantly decreased, while caspase-3 was significantly increased in BPH patients treated with Ser-Se-Ly when compared with the other group. In BPH patients treated with Ser-Se-Ly for 3 months, the glandular epithelium was formed by a single layer of cuboidal cells. PSA showed high immunoexpression in all BPH patients and a focal positivity in Ser-Se-Ly treated patients after 3 months. Evident prostate specific membrane antigen (PSMA) immunoexpression was shown in all BPH patients, while no positivity was present after Ser-Se-Ly administration. Ser-Se-Ly proved to be effective in promoting apoptosis in BPH patients.

Role of PPAR‐α agonist fenofibrate in the treatment of induced benign prostatic hyperplasia with dysplastic changes in rats

“…The development of BPH is closely associated with dysregulation of androgens, increased proliferation and decreased apoptosis of cells in the prostate. This is approved in our study that showed significant decrease of apoptotic marker (caspase3) in group III and this finding is supported by previous studies . Group IV showed highly over expressed caspase3 explaining marked apoptotic features, damage and death of prostatic tissue.…”

Recent Progress in Discovering the Role of Carotenoids and Metabolites in Prostatic Physiology and Pathology—A Review—Part II: Carotenoids in the Human Studies

“…After three months, there was a decrease in survivin and NAIP, while caspase-3 was significantly increased in BPH patients treated with SeR-Se-LYC, in comparison with the placebo group. This combination of compounds also reduced PSA and prostate-specific membrane antigen (PSMA) expression [ 75 ]. It has been hypothesized that SeR, LYC, and Se, administered together, can amplify their therapeutic efficacy also in terms of counteracting the inflammatory component of BPH.…”

Lycopene Attenuates Hypoxia-Induced Testicular Injury by Inhibiting PROK2 Expression and Activating PI3K/AKT/mTOR Pathway in a Varicocele Adult Rat

“…Besides, the reason why varicocele impacted the function of testis and epididymis was still indefinite. Lycopene was reported as a safe nontoxic natural extract with antioxidative and anti-inflammatory effects [6], which was used to treat the chronic prostatitis and/or chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer as a supplementary treatment [7][8][9]. In earlier studies, researchers found that oxidative stress [2] and hypoxia [10] due to varicocele were considered to contribute to the hypoxia-induced testicular injury.…”