ABSTRACT
Insulin-like growth factor-2 binding proteins (IGF2BPs) are oncogenic RNA-binding proteins, highly up-regulated in HCC, and were recently validated as direct targets of the tumour suppressor miR-1275. It is worth noting that around 47% of FDA approved anticancer drugs are derived from plants. Modulation by miRNAs and their cellular signalling cascades could constitute new pathways by which these phytochemicals exert their effects. This study aimed to investigate the potential use of Tamarix articulata, quercetin and epigallocatechin gallate (EGCG) in HCC and how these phytochemicals could epigenetically modulate the IGF axis using their impact on miR-1275. T. articulata ethyl acetate fraction significantly reduced the viability of Huh-7 cells compared to control cells. Treatment with T. articulata ethyl acetate fraction, quercetin and EGCG significantly enhanced miR-1275, while suppressed IGF2BP1 and IGF2BP3 mRNA expression levels. In summary, T. articulata, quercetin and EGCG have important implications for HCC molecular-targeted therapy through destabilizing the interplay between miR-1275 and the IGF axis.
Subject(s)
Carcinoma, Hepatocellular/therapy , Insulin-Like Growth Factor Binding Protein 2/metabolism , Liver Neoplasms/therapy , MicroRNAs/metabolism , Quercetin/therapeutic use , Tamaricaceae/chemistry , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Catechin/analogs & derivatives , Catechin/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Humans , Liver Neoplasms/pathologyABSTRACT
Due to our interest in bioactive plant derived materials, the hepatoprotective activity of the aqueous alcoholic extract of Gentiana spicata AEGS (Gentianaceae) on carbon tetrachloride treated rats was investigated. CCl4 used at a concentration of 1 mL/kg.b.wt. significantly increased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). However, pre-treatment with AEGS and its individual components significantly prevented the increase in these enzymes, which are the major indicators of liver injury. Biochemical assays of liver homogenate showed that AEGS and its components restored reduced glutathione (GSH) depletion reduced the level of thiobarbituric acid reactive substances (TBARS). Furthermore, liver histological observation also showed an obvious amelioration in liver cell necrosis, liver lesions, and fatty changes in pre-treated groups. Phytochemical investigation of the extract showed high phenolic content and led to the isolation and identification of the new carboxygentisic acid, 1,4-dicarboxy 2,5-dihydroxybenzene, for which we suggest the name spicatic acid, together with the known flavonoids, quercetin 3-O-[(2,3,4-triacetyl-α-rhamnopyranosyl)1'''â6''] 3-acetyl-ß-galactopyranoside and quercetin 3-O-[(2,3,4-triacetyl-α-rhamnopyranosyl)1'''â6'']-4-acetyl-ß-galactopyranoside, epicatechin, catechin and their gallolyated derivatives. All structures were elucidated on the basis of conventional analytical methods and confirmed by high resolution ESIMS, 1D- and 2D-NMR data. The new phenolic 4-carboxygentisic acid, spicatic acid is of special interest as it represents the first phenolic acid in nature which bears two carboxyl functions in one aromatic ring.
