J Basic Clin Physiol Pharmacol 2015; aop *Corresponding author: Ganiyu Oboh, Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, Akure, Nigeria, Phone: +2347031388644, E-mail: goboh2001@yahoo.com Ayokunle O. Ademosun: Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, Akure, Nigeria; and Department of Life Sciences, University of Trieste, Trieste, Italy Sabina Passamonti, Federica Tramer and Lovro Ziberna: Department of Life Sciences, University of Trieste, Trieste, Italy Aline Augusti Boligon and Margareth Linde Athayde: Program of Post-Graduation in Pharmaceutical Sciences, Federal University of Santa Maria, Campus Camobi, Santa Maria, RS, Brazil Ayokunle O. Ademosun, Ganiyu Oboh*, Sabina Passamonti, Federica Tramer, Lovro Ziberna, Aline Augusti Boligon and Margareth Linde Athayde Inhibition of metalloproteinase and proteasome activities in colon cancer cells by citrus peel extracts DOI 10.1515/jbcpp-2013-0127 Received August 22, 2013; accepted April 8, 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 mecha- nism by which the peels could manage/prevent colon cancer. Methods: The inhibition of MMP and proteasome activi- ties in the cells by the peel extracts, as well as the identi- fication 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 inhi- bition in LoVo/ADR lysates. Grapefruit had the least pro- teasome 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. Keywords: citrus peels; colon cancer; matrix metallopro- teinase; phenolic extracts; proteasome. Introduction The burden of colorectal cancer, which is the second leading cause of cancer-related death, is further com- pounded by the cost of therapy, which is unbearable for low-income earners and patients in developing countries. This has led to a continuous search for alternative and affordable therapy. A modern approach to the manage- ment of cancers is the use of matrix metalloproteinases (MMPs) and proteasome inhibitors. MMPs are proteolytic enzymes produced by tumor cells to destroy matrix bar- riers and invade into surrounding tissues. Furthermore, MMPs aid angiogenesis and metastasis of tumors by establishing a suitable microenvironment for such [1]. In colorectal cancer, there is increased expression of MMPs, such as MMP-1, MMP-2, MMP-7, MMP-9 and MMP-13, which correlates with phase of the cancer [2]. The development of several cancer types has been linked to “protein degra- dation disorders” caused by defects in the ubiquitin-pro- teasome system (UPS). The UPS, which plays a crucial role in homeostatic balance in the cell through protein degra- dation, has, therefore, become an important therapeutic target in cancer prevention and management. Synthetic proteasome inhibitors have been developed, while more potent ones have been isolated from natural sources. More so, the anticancer effects of some dietary flavonoids have been linked to their proteasome inhibitory ability [3]. In Brought to you by | Carleton University OCUL Authenticated Download Date | 7/16/15 5:48 AM