Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study.
Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated thatSerenoa 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.
Department of Urology, Polyclinic Hospital, University of Catania, 95124 Catania, Italy. gmorgia@policlinico.unict.it.
Giuseppe
G
Morgia
Department of Biomedical Sciences, University of Messina, 98125 Messina, Italy. amicali@unime.it.
Antonio
A
Micali
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Torre Biologica, 5th Floor, Via C. Valeria, Gazzi, 98125 Messina, Italy. mrinaldi@unime.it.
Mariagrazia
M
Rinaldi
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Torre Biologica, 5th Floor, Via C. Valeria, Gazzi, 98125 Messina, Italy. nirrera@unime.it.
Natasha
N
Irrera
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Torre Biologica, 5th Floor, Via C. Valeria, Gazzi, 98125 Messina, Italy. hrmarini@unime.it.
Herbert
H
Marini
Department of Biomedical Sciences, University of Messina, 98125 Messina, Italy. puzzolo@unime.it.
Domenico
D
Puzzolo
Department of Biomedical Sciences, University of Messina, 98125 Messina, Italy. apisani@unime.it.
Antonina
A
Pisani
Department of Urology, Polyclinic Hospital, University of Catania, 95124 Catania, Italy. salvoprivi82@gmail.com.
Salvatore
S
Privitera
Department of Urology, Polyclinic Hospital, University of Catania, 95124 Catania, Italy. giorgioivan@virgilio.it.
Giorgio I
GI
Russo
Department of Urology, Polyclinic Hospital, University of Catania, 95124 Catania, Italy. ciminonello@hotmail.com.
Sebastiano
S
Cimino
Department of Human Pathology, University of Messina, 98125 Messina, Italy. aieni@unime.it.
Antonio
A
Ieni
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Torre Biologica, 5th Floor, Via C. Valeria, Gazzi, 98125 Messina, Italy. vtrichilo@unime.it.
Vincenzo
V
Trichilo
Department of Biomedical Sciences, University of Messina, 98125 Messina, Italy. daltavilla@unime.it.
Domenica
D
Altavilla
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Torre Biologica, 5th Floor, Via C. Valeria, Gazzi, 98125 Messina, Italy. fsquadrito@unime.it.
Francesco
F
Squadrito
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Torre Biologica, 5th Floor, Via C. Valeria, Gazzi, 98125 Messina, Italy. lminutoli@unime.it.
Letteria
L
Minutoli
D000368:Aged; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002338:Carotenoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D000077276:Lycopene; D008297:Male; D008875:Middle Aged; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D011470:Prostatic Hyperplasia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D012643:Selenium / Q000494:pharmacology; D018036:Selenium Compounds / Q000494:pharmacology; D028024:Serenoa / Q000737:chemistry; D000077022:Survivin
D000954:Antigens, Surface; C107489:BIRC5 protein, human; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D010936:Plant Extracts; D018036:Selenium Compounds; D000077022:Survivin; D002338:Carotenoids; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D012643:Selenium; D000077276:Lycopene
BPH; Ser-Se-Ly association; inhibitors of apoptosis proteins