Salvatore Caponnetto

Publications (3)10.96 Total impact

• Article: Parkinson's disease is associated with increased serum levels of macrophage migration inhibitory factor.

  Alessandra Nicoletti, Paolo Fagone, Giulia Donzuso, Katia Mangano, Valeria Dibilio, Salvatore Caponnetto, Klaus Bendtzen, Mario Zappia, Ferdinando Nicoletti
  Cytokine 05/2011; 55(2):165-7. · 3.02 Impact Factor
• Article: HE3286, an orally bioavailable synthetic analogue of an active DHEA metabolite suppresses spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse.

  Michele M Kosiewicz, Dominick L Auci, Paolo Fagone, Katia Mangano, Salvatore Caponnetto, Colleen F Tucker, Nabeel Azeem, Steven K White, James M Frincke, Christopher L Reading, Ferdinando Nicoletti
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  ABSTRACT: 5-Androstene-3β,7β,17β-triol (AET) is a naturally occurring anti-inflammatory adrenal steroid that limits acute and chronic inflammation. HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol) is a synthetic derivative of AET with improved pharmaceutical properties and efficacy in some animal models of autoimmunity. Here, daily oral doses of HE3286 led to a suppression of spontaneous autoimmune diabetes in the non-obese diabetic mouse model of type 1 diabetes mellitus when administered either shortly before or after the first incidence of disease onset. Efficacy was associated with reduced insulitis and a suppression of the pathogenic T helper cell type 1 and type 17 phenotypes in peripheral lymphoid organs. These results demonstrate that daily oral treatment with HE3286 administrated relatively late in the destructive autoimmune process led to a suppression of type 1 diabetes mellitus onset and of the pathological inflammatory status, supporting its clinical evaluation in type 1 diabetes mellitus subjects.
  European journal of pharmacology 02/2011; 658(2-3):257-62. · 2.59 Impact Factor
• Article: In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells.

  Marco Donia, Danijela Maksimovic-Ivanic, Sanja Mijatovic, Marija Mojic, Djordje Miljkovic, Gordana Timotijevic, Paolo Fagone, Salvatore Caponnetto, Yousef Al-Abed, James McCubrey, Stanislava Stosic-Grujicic, Ferdinando Nicoletti
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  ABSTRACT: The NO-derivative of the HIV protease inhibitor saquinavir (Saq-NO) is a nontoxic variant of the parental drug with enhanced anticancer activity on several cell lines. However, it is still unclear whether the p53 status of the target cell might influence the sensitivity to Saq-NO. In this study we evaluated the in vitro and in vivo activity of Saq-NO on the p53-deficient hormone resistant prostate cancer PC-3 cells. We demonstrate that the absence of functional p53 is not essential for the capacity of Saq-NO to reduce prostate cancer cell growth. In contrast to its previously described cytostatic action in B16 and C6 cell lines, Saq-NO exerted cytotoxic effects in PC-3 cells leading to dominant induction of apoptosis and enhanced production of proapoptotic Bim. In addition, differently from saquinavir, Saq-NO restored TRAIL sensitivity that was correlated with increased expression of DR5 independent from ROS/RNS production and YY1 repression. NF-κB activation may be responsible of the Saq-NO induced DR5 expression. Moreover, Saq-NO but not saquinavir, exerted synergistic activity with conventional cytostatic therapy. In agreement with these in vitro studies, Saq-NO inhibited the in vivo growth of PC-3 cells xenotransplants to a greater extent than the parental compound. Taken together, these data indicate that Saq-NO possesses powerful and suitable in vitro and in vivo chemotherapeutic potential to be further studied as a novel drug for the treatment of prostate cancer in the clinical setting.
  Cell cycle (Georgetown, Tex.) 02/2011; 10(3):492-9. · 5.36 Impact Factor