The black Vitis vinifera seed oil saponifiable fraction ameliorates hepatocellular carcinoma in vitro and in vivo via modulating apoptosis and ROS/NF-κB signaling - 04/02/24
Abstract |
To date, no total curative therapy for hepatocellular carcinoma (HCC) is available. This study aimed to evaluate the anticancer effect of black Vitis vinifera (VV) seed oil saponifiable (Sap) fraction (BSap) using five different cancer cell lines. The apoptotic and anti-inflammatory impacts of BSap on the cell line with the highest cytotoxic effect were studied. Furthermore, its therapeutic effect on p-dimethylaminoazobenzene (p-DAB)-induced HCC in mice was investigated. The phenolic and vitamin content, as well as the antiradical activities of BSap, were assessed. BSap demonstrated a greater cytotoxic effect on HepG-2 cells (lowest IC50 and highest SI values) than did the other tested cell lines. BSap showed superior anticancer efficacy to 5-FU on all examined cancer cells, particularly HepG-2 cells, by inducing apoptosis and downregulating NF-κB. In HCC-bearing mice, BSap reduced hepatic lipid peroxidation and boosted GSH levels due to its potent antiradical activities and high reducing power. In addition, it had an apoptotic effect by upregulating p53 and BAX and downregulating Bcl-2 fold expression. Moreover, BSap lowered the fold expression of various crucial HCC-related genes: CD133, ALAD1α1, COX-2, ABCG1, AKT1, Gli, Notch1, and HIF1α. Liver function markers and histopathology showed significant improvements in HCC-bearing mice after BSap administration compared to 5-FU. In silico analysis revealed that the most abundant phenolic and fatty acid ingredients of BSap exhibited competitive inhibitory effects on valuable HCC-associated enzymes (NADPH oxidase, histone deacetylase 1, and sepiapterin reductase). Thus, BSap fraction may be a promising treatment of HCC.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Grape fraction (BSap) was cytotoxic to cancer cells, particularly HepG-2. |
• | It could ameliorate oxidative stress in mice with hepatocellular carcinoma (HCC). |
• | BSap also induced apoptosis in HCC and modulated different related oncogenes. |
• | BSap was predicted to be a competitive inhibitor of NOX2, HDAC1, and SepR. |
• | BSap was found to have superior anticancer potency compared to 5-fluorouracil. |
Abbreviations : AKT1, ALDH1α1, ALP, ALT, ANOVA, AO, AST, BAX, Bcl-2, BSap, c-MYC, COX-2, p-DAB, DMEM, DMSO, DPPH, 2, DTNB 5, EAp, EB, FBS, FITC, 5-FU, GAPDH, γ-GGT, GSO, HCC, HDAC1, HEPES, HIF1α, IACUC, MTA1, MTT, NBD-NOX2, NF-κB, Notch1, PB, PDBePISA, PI, PPI, Prom1, RA, RNS, ROS, SepR, SPSS, TBA, TBARS, VV
Keywords : Black grape saponifiable fraction, HepG-2 cells, HCC, Oxidative stress, Apoptosis, In silico analysis
Plan
Vol 171
Article 116215- février 2024 Retour au numéro
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