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Low molecular weight procyanidins from grape seeds enhance the impact of 5-Fluorouracil chemotherapy on Caco-2 human colon cancer cells.

Cheah KY, Howarth GS, Bindon KA, Kennedy JA, Bastian SE - PLoS ONE (2014)

Bottom Line: 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).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%).

View Article: PubMed Central - PubMed

Affiliation: Wine Science and Business Group, School of Agriculture, Food and Wine, Waite Campus, The University of Adelaide, PMB 1, Glen Osmond, Australia; Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service, North Adelaide, Australia.

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.

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Related in: MedlinePlus

Antioxidant activity of the fractions from immature (A) and mature (B) seed extracts measured by Ferric reducing antioxidant power (FRAP) assay.Results are expressed as mean ± SEM of 3 independent experiments. Statistical analysis was determined by one-way ANOVA with Tukey'spost-hoc test. Values with different letters (a,b,c) in each column are statistically different at P<0.05.
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pone-0098921-g001: Antioxidant activity of the fractions from immature (A) and mature (B) seed extracts measured by Ferric reducing antioxidant power (FRAP) assay.Results are expressed as mean ± SEM of 3 independent experiments. Statistical analysis was determined by one-way ANOVA with Tukey'spost-hoc test. Values with different letters (a,b,c) in each column are statistically different at P<0.05.

Mentions: The antioxidant capacity of seed fractions was measured by the FRAP assay (Figure 1). GSE, which contained a mixture of oligomers and polymers of PCs, was included as a positive control to determine the antioxidant activity of the seed fractions. Compared to GSE (5 mM/g), all the fractions had higher FRAP values, ranging from 5.4–8.8 mM/g. The antioxidant capacity of the fractions decreased in the more polymerized PC fractions. The FRAP values were negatively correlated with mDP (r2 = −0.81, P<0.05).


Low molecular weight procyanidins from grape seeds enhance the impact of 5-Fluorouracil chemotherapy on Caco-2 human colon cancer cells.

Cheah KY, Howarth GS, Bindon KA, Kennedy JA, Bastian SE - PLoS ONE (2014)

Antioxidant activity of the fractions from immature (A) and mature (B) seed extracts measured by Ferric reducing antioxidant power (FRAP) assay.Results are expressed as mean ± SEM of 3 independent experiments. Statistical analysis was determined by one-way ANOVA with Tukey'spost-hoc test. Values with different letters (a,b,c) in each column are statistically different at P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048230&req=5

pone-0098921-g001: Antioxidant activity of the fractions from immature (A) and mature (B) seed extracts measured by Ferric reducing antioxidant power (FRAP) assay.Results are expressed as mean ± SEM of 3 independent experiments. Statistical analysis was determined by one-way ANOVA with Tukey'spost-hoc test. Values with different letters (a,b,c) in each column are statistically different at P<0.05.
Mentions: The antioxidant capacity of seed fractions was measured by the FRAP assay (Figure 1). GSE, which contained a mixture of oligomers and polymers of PCs, was included as a positive control to determine the antioxidant activity of the seed fractions. Compared to GSE (5 mM/g), all the fractions had higher FRAP values, ranging from 5.4–8.8 mM/g. The antioxidant capacity of the fractions decreased in the more polymerized PC fractions. The FRAP values were negatively correlated with mDP (r2 = −0.81, P<0.05).

Bottom Line: 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).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%).

View Article: PubMed Central - PubMed

Affiliation: Wine Science and Business Group, School of Agriculture, Food and Wine, Waite Campus, The University of Adelaide, PMB 1, Glen Osmond, Australia; Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service, North Adelaide, Australia.

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.

Show MeSH
Related in: MedlinePlus