Molecular characterization of the grape seeds extract’s effect against chemically induced liver cancer: In vivo and in vitro analyses

Abstract

The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively. GSE's effects were associated with induced apoptosis, reduced cell proliferation, decreased oxidative stress and down regulation of histone deacetylase activity and inflammation makers, such as cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa B-p65 and p-phosphorylated tumor necrosis factor receptor expressions in liver. GSE treatment also decreased the viability of HepG2 cells and induced early and late apoptosis through activating caspase-3 and Bax. Furthermore, GSE induced G2/M and G1/S cell cycle arrest. The present study provides evidence that the GSE's anticancer effect is mediated through the inhibition of cell proliferation, induction of apoptosis, modulating oxidative damage and suppressing inflammatory response.Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death both in developed and under-developed countries 1 . Chronic infection with hepatitis B and C are the main causes of HCC 2 . Other factors that contribute to the formation of HCC include fatty liver disease, iron overload, alcoholism and exposure to environmental carcinogens 3 . One of the most common carcinogens is diethylnitrosamine (DEN), which is widely used in the surrounding of everyday life, in tobacco, smoke, processed food, gasoline, and cosmetics 4 .Chemoprevention of cancer especially by natural compounds is a promising strategy to protect against various stages of cancer development [5][6][7] . Total plant extracts have been of a particular interest mainly because of the synergistic effects of the cocktail of plant metabolites and their multiple points of intervention during chemoprevention 7,8 . The development of pre-neoplastic foci of altered hepatocytes (FAH) was exploited as short-term bioassays to assess the chemopreventive potential of natural products against cancer formation 9 . Thus, inhibiting or suppressing the development of pre-neoplastic FAH by natural products may lead to diminishing the subsequent progression to liver cancer. One particular plant product that has gained much attention is grape seed extract (GSE). Grapes (Vitis vinifera) are rich in polyphenols, with 60-70% of grape polyphenols being found in the seeds, which are available as a nutraceutical agent. The consumer's interest in GSE has been primarily due to its high content of antioxidants in the form of flavonoids, polyphenols and proanthocyanidins 10,11 . GSE has been shown to posses...

Grape Seed Polyphenols and Fatty Acids of Autochthonous Prokupac Vine Variety from Serbia

“…In order to determine the variables responsible for the separation in the PCA scores, the loading plot A number of studies have been conducted aimed to evaluate various biological activities of grape seed extracts rich in polyphenolic compounds especially proanthocyanidins, e. g., antioxidant, anti-inflammatory, cardioprotective, cytotoxic, hepatoprotective. [9][10][11]17] Therefore, wine pomace and grape seeds as the dominant part of it, represent valuable source of these bioactive compounds that are used in numerous types of products in food and pharmaceutical industry. [18] Therefore, the adequate amount of raw material could be of importance implicating that one of the parameters for selecting the appropriate clone is also number of seeds per berry.…”

Investigation of anti-cancer and migrastatic properties of novel curcumin derivatives on breast and ovarian cancer cell lines

“…Drug toxicity and disease relapse remain as major hurdles in the management of cancer despite having advanced targeted therapies. Plant-derived low toxic phenolic compounds are known to exhibit anti-cancer activity by inducing apoptosis in cancer cells [27, 40, 41]. Curcumin is one such example which exhibits anti-cancer activity against various cancer types [42–47].…”

The Study of Antioxidant Components in Grape Seeds

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