A Possible Antineoplastic Potential of Selective, Irreversible Proteasome Inhibitor, Carfilzomib on Chemically Induced Hepatocarcinogenesis in Rats

• Published in: Journal of biochemical and molecular toxicology 2014-09, Vol.28 (9), p.400-406
• Main Authors: Mansour, Mahmoud A., Aljoufi, Mohammed A., Al-Hosaini, Khaled, Al-Rikabi, Ammar C., Nagi, Mahmoud N.
• Format: Article
• Language: English
• Subjects: alpha-Fetoproteins - metabolism; Animals; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Carfilzomib; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - metabolism; Cryoprotective Agents - adverse effects; Cryoprotective Agents - pharmacology; Dimethyl Sulfoxide - adverse effects; Dimethyl Sulfoxide - pharmacology; Hepatocellular Carcinogenesis; Liver Neoplasms - chemically induced; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 2 - metabolism; Neoplasm Proteins - metabolism; Oligopeptides - pharmacology; Proteasome Inhibitor; Proteasome Inhibitors - pharmacology; Rats; Rats, Wistar
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.21577

ABSTRACT The antineoplastic effect of carfilzomib (CFZ) against chemically induced hepatocarcinogenesis was studied. A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group. Rats in group 1 (control group) were given dimethylsulphoxide (DMSO) (0.4 mL/kg i.p) twice a week for 3 weeks from week 8 to week 10. Animals in groups 2 and 3 were given CFZ (2 and 4 mg/kg i.p) twice a week from week 8 to week 10, respectively. Rats in group 4 were given diethylnitrosamine (DENA) at a dose of 0.01% in drinking water for 10 weeks and received a DMSO (0.4 mL/kg i.p) twice a week from week 8 to week 10. Animals in groups 5 and 6 were given DENA at a dose of 0.01% in drinking water for 10 weeks and treated with CFZ (2 and 4 mg/kg i.p) twice a week from week 8 to week 10, respectively. CFZ succeeded in suppressing the elevated serum tumor marker α‐fetoprotein and carcinoembryonic antigen. The antineoplastic effect of CFZ was also accompanied by normalization of elevated hepatic tissue growth factors, matrix metalloproteinase‐2 and tissue inhibitor of metalloproteinase‐1, and augmentation of hepatic endostatin and metallothionein. A histopathological examination of liver samples treated with CFZ after DENA intoxication correlated with the biochemical observation. Treatment with CFZ confers an antineoplastic activity against chemically induced hepatocarcinogenesis. These findings suggest that CFZ plays a pivotal role in the treatment of hepatocarcinogenesis.