Grape Seed Extract Induces Cell Cycle Arrest and Apoptosis in Human Colon Carcinoma Cells

Abstract

One approach to control colorectal cancer (CRC) is its preventive intervention by dietary agents or those consumed as supplements. However, because most of these products are often consumed by patients as an complementary and alternative medicine practice, a scientific base such as efficacy, mechanism, and standardized preparation needs to be developed. Grape seed extract (GSE) is one such supplement widely consumed by humans for its several health benefits. We reported recently that GSE inhibits CRC cell HT29 growth in culture and nude mice xenograft. Because GSE is available commercially through different vendors, here we assessed whether GSE from 2 different manufacturers produces comparable biological effects in a panel of human CRC cell lines. Our results show that irrespective of source, GSE strongly inhibits LoVo, HT29, and SW480 cell growth, with a G1 arrest in LoVo and HT29 cells but an S and/or G2/M arrest in SW480 cell cycle progression. GSE also induced Cip/p21 levels in all 3 cell lines. Furthermore, an induction of apoptosis was observed in all 3 cell lines by GSE. Taken together, our findings suggest that GSE could be an effective CAM agent against CRC possibly due to its strong growth inhibitory and apoptosis-inducing effects.

ACKNOWLEDGMENTS

This work was supported by Grant RO1 AT003623 from the National Center for Complementary and Alternative Medicine, and the Office of Dietary Supplement, National Institutes of Health, Bethesda, MD. All authors have no personal or financial conflict of interest and have not entered into any agreement that could interfere with our access to the data on the research or on our ability to analyze the data independently, to prepare manuscripts, and to publish them.

Notes

^a Abbreviations are as follows: GSE-I, grape seed extract (from Traco Labs (Champaign, IL); GSE-II, GSE from Kikkoman Corporation (Noda City, Japan); CRC, colorectal cancer. The biological activity of GSE-I and GSE-II was measured in terms of their effects on total cell number and percentage of cell death. The data shown in each case are mean of 3 independent observations with SD and were reproducible in 2 additional independent experiments.

* P < 0.05;

^# P < 0.01;

^$ P < 0.001, control (dimethyl sulfoxide) vs. various GSE-I/GSE-II treatments as indicated in the table.

^b Total cell number × 10⁵.