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Chem Biol Interact ; 308: 120-129, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31129132

ABSTRACT

A preclinical study using DEN-induced HCC rat model was attempted to evaluate the antitumor potential of zolmitriptan (ZOL). The molecular insights were investigated using ELISA, qRT-PCR and Western blot techniques. The result confirmed that the HCC condition was developed in response to lower expressions of caspase 3 and 9 which, in turn, was due to the upstream regulation of iNOS, Bcl-xl and Bcl-2, and downstream regulation of eNOS, BAX, BAD and Cyt C. The treatment with ZOL caused the significant activation of caspase mediated apoptotic signals that could be responsible for its anti-HCC potential. Later, 1H NMR based serum metabolomics study confirmed that ZOL restored the perturbed metabolites associated with DEN-induced HCC. The antineoplastic potential of ZOL was found comparable or to some degree better than the marketed chemotherapeutics, 5-flurouracil.


Subject(s)
Apoptosis/drug effects , Caspase 3/metabolism , Caspase 9/metabolism , Oxazolidinones/pharmacology , Tryptamines/pharmacology , Animals , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cytokines/analysis , Disease Models, Animal , Glutathione/metabolism , Lipids/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Neoplasms/chemically induced , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Oxazolidinones/therapeutic use , Oxidative Stress/drug effects , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Wistar , Tryptamines/therapeutic use , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
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