This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaur, M. Articles by Agarwal, C. Search for Related Content PubMed PubMed Citation Articles by Kaur, M. Articles by Agarwal, C. Related Collections Preclinical Intervention Preclinical Intervention: In Vitro: Drugs, Mechanisms Preclinical Intervention: In Vivo (Animals): Drugs, Nutritional Interventions, Mechanisms

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

Authors' Affiliations: ¹ Department of Pharmaceutical Sciences, School of Pharmacy and ² University of Colorado Cancer Center, University of Colorado at Denver and Health Sciences Center, Denver, Colorado

Requests for reprints: Chapla Agarwal, Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box C238, Denver, CO 80262. Phone: 303-315-1381; Fax: 303-315-6281; E-mail: Chapla.Agarwal{at}uchsc.edu.

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 µg/mL) causes a significant dose- and time-dependent inhibition of cell growth with concomitant increase in cell death. GSE induced G₁ phase cell cycle arrest along with a marked increase in Cip1/p21 protein level and a decrease in G₁ 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.

This article has been cited by other articles:

				K. Chatelain, S. Phippen, J. McCabe, C. A. Teeters, S. O'Malley, and K. Kingsley Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas Evid. Based Complement. Altern. Med., July 23, 2008; (2008) nen047v1. [Abstract] [Full Text] [PDF]

				W. L. Applequist, H. Johnson, and G. Rottinghaus (+)-Catechin, (-)-Epicatechin, and Gallic Acid Content of Seeds of Hybrid Grapes Hardy in Missouri Am. J. Enol. Vitic., March 1, 2008; 59(1): 98 - 102. [Abstract] [Full Text] [PDF]