Grape Seed Extract Inhibits In vitro and In vivo Growth of Human Colorectal Carcinoma Cells

Abstract

Purpose: Accumulating evidences suggest the beneficial effects of fruit-and-vegetable consumption in lowering the risk of various cancers, including colorectal cancer. Herein, we investigated the in vitro and in vivo anticancer effects and associated mechanisms of grape seed extract (GSE), a rich source of proanthocyanidins, against colorectal cancer. Experimental Design: Effects of GSE were examined on human colorectal cancer HT29 and LoVo cells in culture for proliferation, cell cycle progression, and apoptosis. The in vivo effect of oral GSE was examined on HT29 tumor xenograft growth in athymic nude mice. Xenografts were analyzed by immunohistochemistry for proliferation and apoptosis. The molecular changes associated with the biological effects of GSE were analyzed by Western blot analysis. Results: GSE (25-100 Ag/mL) causes a significant dose-and time-dependent inhibition of cell growth with concomitant increase in cell death. GSE induced G 1 phase cell cycle arrest along with a marked increase in Cip1/p21 protein level and a decrease in G 1 phase^associated cyclins and cyclin-dependent kinases. GSE-induced cell death was apoptotic and accompanied by caspase-3 activation. GSE feeding to mice at 200 mg/kg dose showed time-dependent inhibition of tumor growth without any toxicity and accounted for 44% decrease in tumor volume per mouse after 8 weeks of treatment. GSE inhibited cell proliferation but increased apoptotic cell death in tumors. GSE-treated tumors also showed enhanced Cip1/p21 protein levels and poly(ADP-ribose) polymerase cleavage. Conclusions: GSE may be an effective chemopreventive agent against colorectal cancer, and that growth inhibitory and apoptotic effects of GSE against colorectal cancer could be mediated via an up-regulation of Cip1/p21.

Potential roles of longan flower and seed extracts for anti-cancer

“…We selected colorectal cancer as the first subject, because it has been the most common cancer type in Taiwan since 2007, when the dietary behavior of Taiwanese became more westernized [34] . Recent studies have revealed that the water reflux extract of longan flowers is enriched with two major compounds, (-)-epicatechin and proanthocyanidin A2 [26] , which are also found in grape seed extract as active anti-colorectal cancer agents [35,36] . Based on these reports, we proposed that LFE could play a possible role in colorectal cancer (CRC) prevention and treatment.…”

“…The mechanisms of LFE in anti-CRC growth are mainly due to cell-cycle arrest in the S phase and induction of mitochondriamediated apoptosis. Previously, Kaur et al [36] reported that proanthocyanidin-rich grape seed extracts inhibited the proliferation of colorectal cancer cells due to their ability to cease G1-phase arrest of the cell cycle. However, LFE elevated cyclin E levels and downregulated cyclin A levels and arrested CRC cells in the DNA synthesis phase of the cell cycle.…”

“…Caspase 3 was activated by the proteolytic cleavage of upstream apoptosome and the consequent cleavage of substrates such as PARP. Many reports suggest that the activation of caspase 3 is a common event during polyphenolics-induced apoptosis of cancer cells [35][36][37]64] . Our previous study showed that LSE enhances caspase 3 activity in CRC cells and induces apoptosis.…”

Renoprotective Effect of Grape Seed Extract against Oxidative Stress Induced by Gentamicin and Hypercholesterolemia in Rats

“…Condensed tannins are known as proanthocyanidins, which are the most abundant flavonoids present in GSE. 13 GSE demonstrated the strongest antioxidant effects and free radical scavenging ability 14 as well as being anti-inflammatory, 15 anticancer, 16 antibacterial 17 ; it has platelet aggregation inhibiting and metal chelating properties 18 and vasodilatory, immunostimulating, antiallergic, antiviral activates 19 ; it reduced plasma cholesterol in animals fed a high cholesterol diet and that may reduce risk of atherosclerosis. 20 Recently, GSE has been marketed as dietary supplement and advocated for its multiple beneficial properties.…”

Anticancer activity of the “Hardaliye” on HT-29 Cell Line and proliferative activity on CF-1 cell line: Apoptosis and Antioxidant pathway responsive gene expressions

“…Feeding mice with grape seed extract which is rich source of anthocyanidins at a dose of 200 mg/kg has been demonstrated to decrease colorectal tumor 44% in volume after 8 weeks of treatment and also induce apoptosis and cell cycle arrest of colon cancer. In addition, in rats fed with resveratrol orally at a dose of 60 mg/kg for 49 days, precancerous colonic lesions decreased [1][2][3][4].…”