title: A possible antineoplastic potential of selective, irreversible proteasome inhibitor, carfilzomib on chemically induced hepatocarcinogenesis in rats.
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.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, 11426, Saudi Arabia. mansour1960us@yahoo.com.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Mansour
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aljoufi
authors.forename: Khaled
authors.initials: K
authors.lastname: Al-Hosaini
authors.forename: Ammar C
authors.initials: AC
authors.lastname: Al-Rikabi
authors.forename: Mahmoud N
authors.initials: MN
authors.lastname: Nagi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism; D003451:Cryoprotective Agents / Q000009:adverse effects* / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000009:adverse effects* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003451:Cryoprotective Agents; D009363:Neoplasm Proteins; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D000509:alpha-Fetoproteins; C524865:carfilzomib; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; C576840:MMP1 protein, rat; D020781:Matrix Metalloproteinase 1; D004121:Dimethyl Sulfoxide
keywords: Carfilzomib; Hepatocellular Carcinogenesis; Proteasome Inhibitor