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.

Abstract:

: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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Donia M,Mangano K,Fagone P,De Pasquale R,Dinotta F,Coco M,Padron J,Al-Abed Y,Giovanni Lombardo GA,Maksimovic-Ivanic D,Mijatovic S,Zocca MB,Perciavalle V,Stosic-Grujicic S,Nicoletti F

doi

10.3892/or.2012.1840

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

682-8

issue

2

eissn

1021-335X

issn

1791-2431

journal_volume

28

pub_type

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