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Synergistic Combination for Chemoprevention of Hepatocellular Carcinoma: An In Silico and In Vitro Approach
Author(s) -
Mishra Savita,
Katare Deepshikha Pande
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12730
Subject(s) - sorafenib , chalcone , in silico , hepatocellular carcinoma , pharmacology , chemistry , in vitro , mechanism of action , docking (animal) , mtt assay , drug , oxidative stress , vitamin c , biochemistry , cancer research , biology , medicine , stereochemistry , nursing , gene
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 H 2 O 2 . 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 H 2 O 2 . 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.