Synergistic Combination for Chemoprevention of Hepatocellular Carcinoma: An In Silico and In Vitro Approach

Combination therapy is one of the best methods to manage the fatality rate in hepatocellular carcinoma (HCC). This study aimed to formulate a synergistic combination of synthetic and herbal compounds for the treatment of HCC as well as to elucidate a possible signalling mechanism. MTT and enzymatic...

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Bibliographic Details
Published in:Basic & clinical pharmacology & toxicology 2017-06, Vol.120 (6), p.532-540
Main Authors: Mishra, Savita, Katare, Deepshikha Pande
Format: Article
Language:English
Subjects:
Alanine Transaminase - metabolism
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Aspartate Aminotransferases - metabolism
Biotechnology
Carcinoma, Hepatocellular - prevention & control
Chalcone - administration & dosage
Chemoprevention
Docking
Drug Synergism
Enzymes
Hep G2 Cells
Hepatocellular carcinoma
Humans
Hydrogen peroxide
Intoxication
Liver cancer
Liver Neoplasms - prevention & control
Molecular Docking Simulation
Niacinamide - administration & dosage
Niacinamide - analogs & derivatives
Oxidation resistance
Oxidative stress
Oxidative Stress - drug effects
Phenylurea Compounds - administration & dosage
Protein interaction
Protein Interaction Maps
Proteins
Signal transduction
Studies
Synergistic effect
Target recognition
Vitamin K 1 - administration & dosage
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Summary:Combination therapy is one of the best methods to manage the fatality rate in hepatocellular carcinoma (HCC). This study aimed to formulate a synergistic combination of synthetic and herbal compounds for the treatment of HCC as well as to elucidate a possible signalling mechanism. MTT and enzymatic assay were performed to determine the synergistic effect of drug combination (sorafenib, vitamin K1 and trans‐chalcone) on HepG2 cell lines after intoxication with H2O2. Protein–protein interaction and docking studies were performed using Pathwaylinker2.0 and Schrödinger's software application to find out the mechanism of action and major targets for drug combination. The overall in vitro result showed that combination of trans‐chalcone, vitamin K1 and sorafenib (10, 5 and 5 μM concentration, respectively) enhanced the resistance against oxidative stress generated by H2O2. The interaction studies helped in identification of few targets for docking of ligands (trans‐chalcone, vitamin K1 and sorafenib). The study reports the synergistic effects of the formulation that can protect the cells from oxidative stress and restore normal levels of cellular enzymes in HepG2 cell line. We were able to determine the mechanism of action of herbal and synthetic formulation through in silico studies. Finally, docking studies confirmed potential targets for inhibition of hepatocarcinogenesis.
ISSN:1742-7835
1742-7843
DOI:10.1111/bcpt.12730