title: Carvacrol modulates instability of xenobiotic metabolizing enzymes and downregulates the expressions of PCNA, MMP-2, and MMP-9 during diethylnitrosamine-induced hepatocarcinogenesis in rats.
abstract: Hepatocellular carcinoma is the fifth most common malignant tumor in the world, both in terms of incidence and mortality in Asian and Western countries. There are currently limited therapeutic regimens available for effective treatment of this cancer. Carvacrol is a predominant monoterpenoic phenol believed to impede cancer promotion and progression. The present study was conducted to decipher the role of carvacrol during diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male wistar albino rats. Carvacrol (15 mg/kg body weight) suppressed the elevation of serum tumor marker enzymes, carcinoembryonic antigen, and α-feto protein induced by DEN. The activities of phase I enzymes increased markedly during DEN induction, but was found to be significantly lowered upon carvacrol treatment. On the contrary, the phase II enzymes decreased in DEN-administered animals, which was improved normalcy upon carvacrol-treated animals. DEN-administered animals showed increased mast cell counts, argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen, and matrix metalloproteinases (MMPs-2/9), whereas carvacrol supplementation considerably suppressed all the above abnormalities. The results suggest that the carvacrol exhibited the potential anticancer activity by inhibiting cell proliferation and preventing metastasis in DEN-induced hepatocellular carcinogenesis.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, Tamilnadu, India.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Subramaniyan
authors.forename: Gokuladhas
authors.initials: G
authors.lastname: Krishnan
authors.forename: Rajan
authors.initials: R
authors.lastname: Balan
authors.forename: Divya
authors.initials: D
authors.lastname: Mgj
authors.forename: Elamaran
authors.initials: E
authors.lastname: Ramasamy
authors.forename: Shenbhagaraman
authors.initials: S
authors.lastname: Ramalingam
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Veerabathiran
authors.forename: Premkumar
authors.initials: P
authors.lastname: Thandavamoorthy
authors.forename: Gopi Krishnan
authors.initials: GK
authors.lastname: Mani
authors.forename: Devaki
authors.initials: D
authors.lastname: Thiruvengadam
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D000081007:Cymenes; D004052:Diethylnitrosamine; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D039821:Monoterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000081007:Cymenes; D039821:Monoterpenes; D018809:Proliferating Cell Nuclear Antigen; D004052:Diethylnitrosamine; C073316:carvacrol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9