Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative             of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation             of A375 human melanoma cells.
We have recently shown that covalent attachment of the nitric oxide (NO)             moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively             new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties             and reduced toxicity both in vitro and in vivo. The aim of this study was to address             several unanswered questions both on the pharmacological profile of Saq-NO as             well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells.             To this end, we have evaluated here the impact of single and combined effects             of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the             in vitro as well as in vivo growth of the iNOS positive A375 cells. Our data confirm             clear-cut evidence for a strong and powerful anti-melanoma action of Saq-NO that             is not duplicable by the combined use of Saq and DETA NONOate. Surprisingly, but             also in agreement with the complex and multifaceted role of endogenous NO in A375             cells, both DETA NONOate and L-NAME significantly suppressed the in vivo growth             of xenotransplants.
Department of Bio-Medical Sciences, University of Catania, and Department of Plastic and Reconstructive Surgery, Cannizzaro Hospital, Catania, Italy.
Marco
M
Donia
Katia
K
Mangano
Paolo
P
Fagone
Rocco
R
De Pasquale
Franco
F
Dinotta
Marinella
M
Coco
Julio
J
Padron
Yousef
Y
Al-Abed
Giuseppe Angelo
GA
Giovanni Lombardo
Danijela
D
Maksimovic-Ivanic
Sanja
S
Mijatovic
Mai-Britt
MB
Zocca
Vincenzo
V
Perciavalle
Stanislava
S
Stosic-Grujicic
Ferdinando
F
Nicoletti
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019258:Saquinavir / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; C557004:saquinavir-NO; D019258:Saquinavir