The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents 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 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.
Donia
Marco
M
Department of Biomedical Sciences, University of Catania, Italy.
Mijatovic
Sanja
S
Maksimovic-Ivanic
Danijela
D
Miljkovic
Djordje
D
Mangano
Katia
K
Tumino
Salvatore
S
Biondi
Antonio
A
Basile
Francesco
F
Al-Abed
Yousef
Y
Stosic-Grujicic
Stanislava
S
Nicoletti
Ferdinando
F
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A; D005260:Female; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous
C518641:3-phenyl-4,5-dihydro-5-isoxazole acetic acid; D000085:Acetates; D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; D010080:Oxazoles; D003208:Concanavalin A