Low Molecular Weight Procyanidins from Grape Seeds Enhance the Impact of 5-Fluorouracil Chemotherapy on Caco-2 Human Colon Cancer CellsReport as inadecuate




Low Molecular Weight Procyanidins from Grape Seeds Enhance the Impact of 5-Fluorouracil Chemotherapy on Caco-2 Human Colon Cancer Cells - Download this document for free, or read online. Document in PDF available to download.

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 F4not 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.



Author: Ker Y. Cheah, Gordon S. Howarth, Keren A. Bindon, James A. Kennedy, Susan E. P. Bastian

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents