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.
Keywords:
(1)H-NMR based metabolomics; Hepatocellular carcinoma; Mitochondrial apoptosis; Zolmitriptan.
Copyright © 2019 Elsevier B.V. All rights reserved.
MeSH terms
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Animals
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Apoptosis / drug effects*
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Carcinoma, Hepatocellular / chemically induced
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / pathology
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Caspase 3 / metabolism*
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Caspase 9 / metabolism*
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Cytokines / analysis
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Disease Models, Animal
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Glutathione / metabolism
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Lipids / blood
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Liver / drug effects
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Liver / metabolism
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Liver / pathology
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Liver Neoplasms / chemically induced
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Liver Neoplasms / drug therapy
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Liver Neoplasms / pathology
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Male
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Oxazolidinones / pharmacology*
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Oxazolidinones / therapeutic use
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Oxidative Stress / drug effects
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Rats
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Rats, Wistar
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Tryptamines / pharmacology*
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Tryptamines / therapeutic use
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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Cytokines
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Lipids
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Oxazolidinones
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Proto-Oncogene Proteins c-bcl-2
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Tryptamines
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bcl-2-Associated X Protein
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zolmitriptan
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Nitric Oxide Synthase Type II
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Caspase 3
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Caspase 9
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Glutathione