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

  • Ayokunle O. Ademosun , Ganiyu Oboh EMAIL logo , Sabina Passamonti , Federica Tramer , Lovro Ziberna , Aline Augusti Boligon and Margareth Linde Athayde
Published/Copyright: June 1, 2015

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.


Corresponding author: Ganiyu Oboh, Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, Akure, Nigeria, Phone: +2347031388644, E-mail:

Acknowledgments

This work was supported in part by the European Regional Development Fund, Cross-Border Cooperation Italy-Slovenia Programme 2007–2013 (EU strategic project TRANS2CARE). Ayokunle O. Ademosun’s stay in Italy was funded by Education Trust Fund (ETF) of the Federal Government of Nigeria/Federal University of Technology, Akure and Training and Research in Italian Laboratory (TRIL) Programme of the Abdus Salam International Centre for Theoretical Physics, Trieste, Italy.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Herszényi L, Hritz I, Lakatos G, Varga MZ, Tulassay Z. The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci 2012;13:13240–63.10.3390/ijms131013240Search in Google Scholar

2. Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 2006;25:9–34.10.1007/s10555-006-7886-9Search in Google Scholar

3. Chen D, Daniel KG, Chen MS, Kuhn DJ, Landis-Piwowar KR, Dou QP. Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells Biochem Pharmacol 2005;69:1421–32.10.1016/j.bcp.2005.02.022Search in Google Scholar

4. Oboh G, Ademosun AO. Characterization of the antioxidant properties of phenolic extracts from some citrus peels. J Food Sci Technol 2012;49:729–36.10.1007/s13197-010-0222-ySearch in Google Scholar

5. Xu GH, Chen JC, Liu DH, Zhang YH, Jiang P, Ye XQ. Minerals phenolic compounds and antioxidant capacity of citrus peel extract by hot water. J Food Sci 2008;73:C11–8.10.1111/j.1750-3841.2007.00546.xSearch in Google Scholar

6. Seki T, Kamiya T, Furukawa K, Azumi M, Ishizuka S, Takayama S, et al. Nobiletin-rich citrus reticulata peels a kampo medicine for Alzheimer’s disease: a case series. Geriatr Gerontol Int 2013;13:236–8.10.1111/j.1447-0594.2012.00892.xSearch in Google Scholar

7. Chu Y, Sun J, Wu X, Liu RH. Antioxidant and antiproliferative activity of common vegetables. J Agric Food Chem 2002;50:6910–6.10.1021/jf020665fSearch in Google Scholar

8. Knight CG, Willenbrock F, Murphy G. A novel coumarin-labelled peptide for sensitive continuous assays of the matrix metalloproteinases. FEBS Lett 1992;296:263–6.10.1016/0014-5793(92)80300-6Search in Google Scholar

9. Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res 2008;68:7283–92.10.1158/0008-5472.CAN-07-6246Search in Google Scholar PubMed PubMed Central

10. Amaral GP, Carvalho NR, Barcelos RP, Dobrachinski F, Portella RL, da Silva M, et al. Protective action of ethanolic extract of Rosmarinus officinalis L in gastric ulcer prevention induced by ethanol in rats. Food Chem Toxicol 2013;55:48–55.10.1016/j.fct.2012.12.038Search in Google Scholar PubMed

11. Sabir SM, Ahmad SD, Hamid A, Khan MQ, Athayde ML, Santos DB, et al. Antioxidant and hepatoprotective activity of ethanolic extract of leaves of Solidago microglossa containing polyphenolic compounds. Food Chem 2012;131:741–7.10.1016/j.foodchem.2011.09.026Search in Google Scholar

12. Zar JH. Biostatistical analysis. New Jersey, USA: Prentice-Hall Inc., 1984:620.Search in Google Scholar

13. Rundhaug JE. Matrix metalloproteinases, angiogenesis and cancer. Clin Cancer Res 2003;9:551–4.Search in Google Scholar

14. Figueira RC, Gomes LR, Neto JS, Silva FC, Silva ID, Sogayar MC. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer 2009;9:20.10.1186/1471-2407-9-20Search in Google Scholar PubMed PubMed Central

15. Chen HJ, Lin CM, Lee CY, Shih NC, Peng SF, Tsuzuki M, et al. Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells. Oncol Rep 2013;30:925–32.10.3892/or.2013.2490Search in Google Scholar PubMed

16. Sim GS, Lee BC, Cho HS, Lee JW, Kim JH, Lee DH, et al. Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast. Arch Pharma Res 2007;30:290–8.10.1007/BF02977608Search in Google Scholar PubMed

17. Lee EJ, Kim DI, Kim WJ, Moon SK. Naringin inhibits matrix metalloproteinase-9 expression and AKT phosphorylation in tumor necrosis factor-α-induced vascular smooth muscle cells. Mol Nutr Food Res 2009;53:1582–91.10.1002/mnfr.200800210Search in Google Scholar PubMed

18. Sang QA, Jin Y, Newcomer RG, Monroe SC, Fang X, Hurst DR, et al. Matrix metalloproteinase inhibitors as prospective agents for the prevention and treatment of cardiovascular and neoplastic diseases. Curr Top Med Chem 2006;6:289–316.10.2174/156802606776287045Search in Google Scholar PubMed

19. Huang HP, Shih YW, Chang YC, Hung CN, Wang CJ. Chemoinhibitory effect of mulberry anthocyanins on melanoma metastasis involved in the Ras/PI3K pathway. J Agric Food Chem 2008;56:9286–93.10.1021/jf8013102Search in Google Scholar PubMed

20. Matchett MD, MacKinnon SL, Sweeney MI, Gottschall-Pass KT, Hurta RA. Inhibition of matrix metalloproteinase activity in DU145 human prostate cancer cells by flavonoids from lowbush blueberry (Vaccinium angustifolium): possible roles for protein kinase C and mitogen-activated protein-kinase-mediated events. J Nutr Biochem 2006;17:117–25.10.1016/j.jnutbio.2005.05.014Search in Google Scholar PubMed

21. Voorhees PM, Dees EC, O’Neil B, Orlowski1 RZ. The proteasome as a target for cancer therapy. Clin Cancer Res 2003;9:6316–25.Search in Google Scholar

Received: 2013-8-22
Accepted: 2015-4-8
Published Online: 2015-6-1
Published in Print: 2015-9-1

©2015 by De Gruyter

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