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.

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.

THE NOVEL NO-DONATING COMPOUND GIT-27NO INHIBITS IN VIVO GROWTH OF HUMAN PROSTATE CANCER CELLS AND PREVENTS MURINE IMMUNOINFLAMMATORY HEPATITIS

MANGANO, KATIA DOMENICA;TUMINO, Salvatore;BIONDI, Antonio Giuseppe;BASILE, Francesco;NICOLETTI, FERDINANDO
2009

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/8243
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