The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis
Article (Published version)
MetadataShow full item record
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 PO 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 Grr-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis. (C) 2009 Elsevier B.V. All rights reserved.