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  • Inhibition of metalloproteinase and proteasome activities in colon cancer cells by citrus peel extracts.

Inhibition of metalloproteinase and proteasome activities in colon cancer cells by citrus peel extracts.

Journal of basic and clinical physiology and pharmacology (2015-06-02)
Ayokunle O Ademosun, Ganiyu Oboh, Sabina Passamonti, Federica Tramer, Lovro Ziberna, Aline Augusti Boligon, Margareth Linde Athayde
ABSTRACT

Citrus peels are consumed in the form of infusions, candy or wine, based on their well-documented nutritional and medicinal properties. This study sought to investigate the effect of some citrus peels' [grapefruit (Citrus paradisii), orange (Citrus sinensis) and shaddock (Citrus maxima)] extracts on matrix metalloproteinase (MMP) and proteasome activities in primary human colonic tumor (Caco-2) and the metastatic cell lines (LoVo and LoVo/ADR) in a bid to explain the possible mechanism by which the peels could manage/prevent colon cancer. The inhibition of MMP and proteasome activities in the cells by the peel extracts, as well as the identification of phenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD), was determined. Orange peel extracts had the strongest inhibition of MMP in Caco-2 and LoVo cells, while shaddock had the least. Shaddock peel extracts also had the least MMP inhibition in LoVo/ADR lysates. Grapefruit had the least proteasome inhibition in Caco-2 and LoVo lysates, while there was no significant (p>0.05) difference in the proteasome inhibition of the peel extracts in LoVo/ADR lysates. The extracts inhibited proteasome activity in extract-treated cells, and HPLC fingerprinting of the extracts revealed the presence of some phenolic compounds such as quercetin, caffeic acid, kaempferol, catechin and naringin. The inhibition of MMP and proteasome activities in colon cancer cell lines suggests the potential use of citrus peels as functional food in the management and/or prevention of colon cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Quercetin, ≥95% (HPLC), solid
Sigma-Aldrich
Quercetin 3-β-D-glucoside, ≥90% (HPLC)
Sigma-Aldrich
Kaempferol, ≥97.0% (HPLC)
Sigma-Aldrich
Acetone, natural, ≥97%
Sigma-Aldrich
Acetone, ≥99%, meets FCC analytical specifications
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Sodium pyruvate, BioXtra, ≥99%
Sigma-Aldrich
Kaempferol, ≥90% (HPLC), powder
Sigma-Aldrich
Sodium pyruvate, powder, BioXtra, suitable for mouse embryo cell culture
Sigma-Aldrich
Sodium pyruvate, Hybri-Max, powder, suitable for hybridoma
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
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Sodium pyruvate, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%
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Sodium pyruvate, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
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Sodium pyruvate, ReagentPlus®, ≥99%
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Dimethyl sulfoxide, Vetec, reagent grade, 99%
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
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8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
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L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
SAFC
L-Glutamine
Sigma-Aldrich
Naringin, ≥95% (HPLC)
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Caffeic acid, ≥98.0% (HPLC)
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
3-Hydroxyflavone, ≥98%
Sigma-Aldrich
Naringin, ≥90% (HPLC), from citrus fruit