EFFETTO DELLA SERENOA REPENS (PERMIXON) SULL’ESPRESSIONE DEI GENI CORRELATI ALL’INFIAMMAZIONE E SULL’ ATTIVAZIONE DELL’NFKB IN COLTURE PRIMARIE DI CARCINOMA PROSTATICO Silvestri I, Cattarino S, Aglianò AM, Scarpa S, Salciccia S, Innocenzi M, Minisola F, Frati L, Gentile V, Sciarra A. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy Department of Obstretics, Gynecology and Urological Science, “Sapienza” University, Rome, Italy

Background May inflammation significantly condition the development and future progression of prostate diseases

Background

Background Vacherot F et al, Prostate 2000, 45:259-66

SERENOA REPENS (PERMIXON®)

Aim of the study Analizzare l’espressione di citochine e chemochine infiammatorie e l’attivazione dell’NFKB in linee cellulari PC3 e LNCaP e per la prima volta in colture cellulari primarie di carcinoma prostatico. Analizzare l’effetto della Serenoa Repens (Permixon) su tali fattori determinando l’effetto del farmaco sul processo proliferativo-apoptotico, correlandolo con l’espressione infiammatoria e l’attivazione dell’NFKB. Colture Primarie

Material and Methods LNCaP PC3 Colture primarie (40 pt sottoposti a RRP ) Proliferazione e apoptosi Conta cellulare e Caspasi 3 NF-kB Immunofluoresecenza Pre e post TRATTAMENTO 44 e 88 microg/ml a 16,24,48,72 hr Geni infiammazione RT-PCR

Results 1) PC3 e LNCaP <<< post trattemento 2) Colture primarie <<< post trattamento 3) Attivazione della CASPASi: >>> Apoptosi

Results 4) <<< di IL-6, CCL-5 CCL-2, COX-1, iNOS 5) Traslocazione NFkB

Discussion CJ Loveridge, ADH MacDonald, HC Thoms, MG Dunlop and LA Stark The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-jB Oncogene (2008) 27, 2648–2655 Sweeney et al. Nuclear factor-kappaB is constitutively activated in prostate cancer in vitro and is overexpressed in prostate intraepithelial neoplasia and adenocarcinoma of the prostate. Clin Can Res 2004, August; Vol 10, Apoptosi-proliferazione Geni infiammazione NFKB

Conclusions Our study contributes to a better understanding of the effect of inflammatory-related genes on PC cell growth and the potential inhibitory effect of LSESr (Permixon) on these pathways. In particular, using primary cultures from human PC tissue, we showed that the inhibitory effect of LSESr (Permixon) on cell growth could be in part associated to the down-regulation of inflammatory-related genes and to the activation of NF-kB pathway in prostate tissue.