Effect of Grape Seed Extract (vitis vinifera, sp) on Histopathology Appearance, CMYC and BCL-2 Gene Expression of AOM-DSS Induced Mice (original) (raw)
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Suppression of colon carcinogenesis by bioactive compounds in grapefruit
Carcinogenesis, 2006
This study evaluated the hypothesis that untreated and irradiated grapefruit as well as the isolated citrus compounds naringin and limonin would protect against azoxymethane (AOM)-induced aberrant crypt foci (ACF) by suppressing proliferation and elevating apoptosis through anti-inflammatory activities. Male Sprague-Dawley rats (n ¼ 100) were provided one of five diets: control (without added grapefruit components), untreated or irradiated (300 Gy, 137 Cs) grapefruit pulp powder (13.7 g/kg), naringin (200 mg/kg) or limonin (200 mg/kg). Rats were injected with saline or AOM (15 mg/kg) during the third and fourth week and colons were resected (6 weeks post second injection) for evaluation of ACF, proliferation, apoptosis, and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein levels. Experimental diets had no effect on the variables measured in saline-injected rats. However, in AOM-injected rats, the experimental diets suppressed (P 0.02) aberrant crypt and high multiplicity ACF (HMACF; P 0.01) formation and the proliferative index (P 0.02) compared with the control diet. Only untreated grapefruit and limonin suppressed (P 0.04) HMACF/cm and expansion (P 0.008) of the proliferative zone that occurred in the AOM-injected rats consuming the control diet. All diets elevated (P 0.05) the apoptotic index in AOM-injected rats, compared with the control diet; however, the greatest enhancement was seen with untreated grapefruit and limonin. Untreated grapefruit and limonin diets suppressed elevation of both iNOS (P 0.003) and COX-2 (P 0.032) levels observed in AOM-injected rats consuming the control diet. Although irradiated grapefruit and naringin suppressed iNOS levels in AOM-injected rats, no effect was observed with respect to COX-2 levels. Thus, lower levels of iNOS and COX-2 are associated with suppression of proliferation and upregulation of apoptosis, which may have contributed to a decrease in the number of HMACF in rats provided with untreated grapefruit and limonin. These results suggest that consumption of grapefruit or limonin may help to suppress colon cancer development.
Antiproliferative and apoptotic effects of Grape Seed Extract on human colon cancer cell line HCT116
Grape seed extract (GSE) has been proven to inhibit cell proliferation and induce apoptosis in various human carcinoma cell lines. Herein, we evaluated the in vitro antiproliferative and apoptotic effects of GSE against colon cancer cell line HCT116. The cytotoxic effect of GSE was examined on human colon cancer HCT116 and normal WISH cells. In addition, we evaluated the antiproliferative and apoptotic effects of different concentrations of GSE (25, 50 and 100µg/ml) at different sampling time (24, 48, 72 and 96hrs) on HCT116 cells using cell proliferation and DNA fragmentation assays respectively. Because the p53 tumor suppressor protein plays an important role in cellular proliferation and apoptosis, we examined p53 mRNAs expression in relation with BAX and BCL-2 mRNAs expression. The present study revealed that GSE did not suppress the proliferation of normal human WISH cells, while, GSE suppressed proliferation and induced apoptosis in human HCT116 colon cancer cells indicating t...
2013
Colon cancer is a common cause of cancer-related mortality. 5-fluorouracil (5-FU) is the reference regimen alone or as a combined therapy in colon cancer treatment. Despite the excellent chemotherapeutic effect of 5-FU, its toxicity in normal cells remains a major problem. Recently, the use of natural substances as cancer preventative or therapeutic agents has become a worldwide trend. Grape seed extract (GSE) is a potent chemopreventive agent against colon cancer both in vitro and in vivo. In order to prepare for a human trial, we conducted a study with GSE as a chemotherapeutic agent in an O-Nitrotoluene (O-NT)-induced precancerous stage in mice colon. To compare the efficacy of either 5-FU or GSE in treatment of precancerous stage of colon, male albino mice were administrated O-NT (150mg/kg) orally three times a week for six consecutive weeks followed by orally administration of Low dose (150mg/kg, LGSE) or high dose (300mg/kg, HGSE) GSE daily for one, two and three consecutive m...
Scientific Reports
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 underdeveloped 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 5-7. 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 possess potent cardioprotective, hepatoprotective, antidiabetic, anti-mutagenic and anti-inflammatory properties 10-12. Moreover, GSE has shown promising chemopreventive and anticancer effects in various cancer
BMC complementary and alternative medicine, 2016
We have previously shown that the grape bioactive compound resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell apoptosis at physiologically relevant concentrations. However, RSV-GSE combination efficacy against colon cancer stem cells (CSCs), which play a key role in chemotherapy and radiation resistance, is not known. We tested the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human colon CSCs in vitro and an azoxymethane-induced mouse model of colon carcinogenesis in vivo. RSV-GSE suppressed tumor incidence similar to sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed - proliferation, sphere formation, nuclear translocation of β-catenin (a critical regulator of CSC proliferation) similar to sulindac in isolated human colon CSCs. RSV-GSE, but not s...
International Journal of Molecular Sciences, 2012
Grape seed extract has been proven to exert anticancer effects on different tumors. These effects are mainly ascribed to catechin and procyanidin content. Analytical studies demonstrated that grape seed extract composition is complex and it is likely other components could exert biological activities. Using cell count and flow cytometry assays, we evaluated the cytostatic and apoptotic effects produced by three different grape seed extracts from Italia, Palieri and Red Globe cultivars, on Caco2 and HCT-8 colon cancer cells. These effects were compared to those induced by epigallocatechin and procyanidins, alone or in association, on the same cell lines. All the extracts induced growth inhibition and apoptosis in Caco2 and HCT-8 cells, along the intrinsic apoptotic pathway. On both OPEN ACCESS
The Journal of nutrition, 2004
Many popular dietary supplements are enriched in polyphenols such as the soy isoflavones, tea catechins, and resveratrol (from grape skins), each of which has been shown to have chemopreventive activity in cellular models of cancer. The proanthocyanidins, which are oligomers of the catechins, are enriched in grape seeds and form the basis of the dietary supplement grape seed extract (GSE). Evidence suggests that the proanthocyanidins may be metabolized to the monomeric catechins. This study was carried out to determine whether GSE added to rodent diets protected against carcinogen-induced mammary tumorigenesis in rats and whether this was affected by the composition of the whole diet. Female rats were begun on 5%, 1.25%, or 0% (control) GSE-supplemented diets at age 35 d. At age 50 d they were administered 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil at 80 mg/kg body weight. They were weighed and monitored weekly for tumor development until 120 d after DMBA administration. Ad...
Asian Pacific journal of cancer prevention : APJCP, 2015
The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF- α. Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF- kB, TNF- and iNOS was evaluated by qPCR. The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF- α and NF-kB gene expression (p=0.002). In conclusion, the...