The novel NO-donating compound GIT-27NO inhibits in vivo

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• 作者：Marco Donia ; Sanja Mijatovic ; Danijela Maksimovic-Ivanic ; Djordje Miljkovic ; Katia Mangano ; Salvatore Tumino ; Antonio Biondi ; Francesco Basile ; Yousef Al-Abed ; Stanislava Stosic-Grujicic ; Ferdin ; o Nic
• 关键词：Cancer ; GIT-27NO ; Hepatitis ; Nitric oxide ; Nitric oxide donors ; Prostate cancer
• 刊名：European Journal of Pharmacology
• 出版年：2009
• 出版时间：1 August 2009
• 年：2009
• 卷：615
• 期：1-3
• 页码：228-233
• 全文大小：612 K

文摘

We investigated the effects of the recently synthetized NO donating agent GIT-27NO on the growth of human androgen independent and androgen dependent PC3 and LnCap cells xenografted in nude mice. We also tested the effects of GIT-27NO in the preclinical model of cell-mediated immunoinflammatory hepatitis that can be induced in mice by Concanavalin A (ConA) and that has been shown to benefit from the treatment with NO donating agents such as NO-aspirin. In agreement with in vitro data showing dose-dependent reduction of PC3 and LnCap cell viability with GIT-27NO, the i.p. treatment of mice xenografted with either of these cells with GIT-27NO significantly inhibited their growth as compared to the mice-treated with its vehicle. In addition, GIT-27NO given − 24 and − 1 h prior to e.v. challenge with 20 mg/kg ConA significantly suppressed the increase of transaminases that occurred 8 h after challenge in the control mice that received the vehicle. In addition, relative to these latter groups of mice, the histological signs of inflammatory hepatitis were markedly reduced in ConA-challenged mice that received GIT-27NO. In the hepatitis model, GIT-27NO was equally effective in preventing ConA-induced hepatitis regardless of whether it was administered intra peritoneally or per os. These data confirm that GIT-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis.