Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/87602
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Low molecular weight procyanidins from grape seeds enhance the impact of 5-Fluorouracil chemotherapy on Caco-2 human colon cancer cells |
Author: | Cheah, K. Howarth, G. Bindon, K. Kennedy, J. Bastian, S. |
Citation: | PLoS One, 2014; 9(6):e98921-1-e98921-8 |
Publisher: | Public Library of Science |
Issue Date: | 2014 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Samant, R. |
Statement of Responsibility: | Ker Y. Cheah, Gordon S. Howarth, Keren A. Bindon, James A. Kennedy, Susan E. P. Bastian |
Abstract: | OBJECTIVE: Grape seed procyanidins (PC) are flavan-3-ol oligomers and polymers known for their biological activity in the gut. Grape seed extract (GSE) have been reported to reduce intestinal injury in a rat model of mucositis. We sought to investigate effects of purified PC fractions differing in mean degree of polymerization (mDP) combined with 5-Fluorouracil (5-FU) chemotherapy on the viability of colon cancer cells (Caco-2). DESIGN: SixPC fractions (F1-F6) were isolated from Cabernet Sauvignon seeds at two ripeness stages: pre-veraison unripe (immature) and ripe (mature), utilizing step gradient, low-pressure chromatography on a Sephadex LH-20 resin. Fractions were tested on Caco-2 cells, alone and in combination with 5-FU. Eluted fractions were characterized by phloroglucinolysis and gel permeation chromatography. Cell viability was determined by the 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) (MTT) assay. RESULTS: All isolated fractions significantly reduced Caco-2 cell viability compared to the control (P<0.05), but F2 and F3 (mDP 2-6) were the most active fractions (immature F2 = 32% mDP 2.4, F3 = 35% mDP 5.8 and mature F2 = 13% mDP 3.6 and F3 = 17% mDP 5.9; percentage of viable cells remaining) on Caco-2 cells. When combined with 5-FU, immature fractions F1-F3 enhanced the cell toxicity effects of 5-FU by 27-73% (P<0.05). Mature seed PC fractions (F1-F4) significantly enhanced the toxicity of 5-FU by 60-83% against Caco-2 cells (P<0.05). Moreover, some fractions alone were more potent at decreasing viability in Caco-2 cells (P<0.05; immature fractions = 65-68% and mature fractions = 83-87%) compared to 5-FU alone (37%). CONCLUSIONS: PCs of mDP 2-6 (immature F1-F3 and mature F1 and F4)not only enhanced the impact of 5-FU in killing Caco-2 cells, but also surpassed standard 5-FU chemotherapy as an anti-cancer agent.The bioactivity of PC is therefore attributed primarily to lower molecular weight PCs. |
Keywords: | Caco-2 Cells Humans Colonic Neoplasms Fluorouracil Catechin Biflavonoids Proanthocyanidins Antineoplastic Agents Antioxidants Cell Survival Drug Synergism Molecular Weight Grape Seed Extract |
Rights: | © 2014 Cheah et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0098921 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0098921 |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest 7 |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_87602.pdf | Published version | 450.65 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.