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http://dx.doi.org/10.5352/JLS.2010.20.4.528

Effects of Aged Black Garlic Extracts on the Tight Junction Permeability and Cell Invasion in Human Gastric Cancer Cells  

Shin, Dong-Yeok (Department of Biochemistry, College of Oriental Medicine, Dongeui University)
Yoon, Moo-Kyoung (Vegetable Research Division, National Institute of Horticulture & Herbal Science)
Choi, Young-Whan (Department of Horticultural Bioscience, College of Natural Resource and Life Sciences, Pusan National University)
Gweon, Oh-Cheon (Department of Hotel Culinary Arts & Bakery, Gyeongnam Provincial Namhae College)
Kim, Jung-In (School of Food and Life Science, Inje University)
Choi, Tae-Hyun (Department of Ophthalmic Optics, Daegu Technical University)
Choi, Yung-Hyun (Department of Biochemistry, College of Oriental Medicine, Dongeui University)
Publication Information
Journal of Life Science / v.20, no.4, 2010 , pp. 528-534 More about this Journal
Abstract
Garlic (Allium sativum) has been well-known as a folk remedy for a variety of ailments since ancient times, and it is well documented that enhanced garlic consumption leads to a decrease in incidences of cancer. Tight junctions (TJs) are critical structures for the maintenance of cellular polarity, acting as paracellular permeability barriers and playing an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. Matrix metalloproteinases (MMPs) have been implicated as possible mediators of invasiveness and metastasis in some cancers. In this study, we investigated the potential effects of water extract of aged black garlic (ABG) on the correlation between tightening of TJs and anti-invasive activity in human gastric carcinoma AGS cells. The inhibitory effects of ABG on cell motility and invasiveness were found to be associated with increased tightness of TJs, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, the activities of MMP-2 and -9 in AGS cells were inhibited by treatment with ABG, and this was also correlated with a decrease in the expression of their mRNA and proteins. Furthermore, RT-PCR and immunoblotting results indicated that ABG repressed the levels of the claudin proteins, major components of TJs that play a key role in the control and selectivity of paracellular transport. In conclusion, these results suggest that ABG treatment may inhibit tumor metastasis and invasion, and therefore may act as a dietary source to decrease the risk of developing cancer.
Keywords
Aged black garlic; tight junction; MMP; invasion;
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1 Yokoyama, K., N. Kamata, E. Hayashi, T. Hoteiya, N. Ueda, R. Fujimoto, and M. Ngayama. 2001. Reverse correlation of E-cadherin and snail expression in oral squamous cell carcinoma cells in vitro. Oral. Oncol. 37, 65-71.   DOI
2 Peralta, S. A., J. M. Mullin, K. A. Knudsen, and C. W. Marano. 1996. Tissue remodeling during tumor necrosis factor-induced apoptosis in LLC-PK1 renal epithelial cells. Am. J. Physiol. 270, F869-F879.
3 Rawlings, N. D. and A. J. Barrett. 1995. Evolutionary families of metallopeptidases, Methods Enzymol. 248, 183-228.   DOI
4 Riehl, T. E. and W. F. Stenson. 1994. Mechanisms of transit of lipid mediators of inflammation and bacterial peptides across intestinal epithelia. Am. J. Physiol. 267, G687-G695.
5 Khanum, F., K. R. Anilakumar, and K. R. Viswanathan. 2004. Anticarcinogenic properties of garlic: a review. Crit. Rev. Food Sci. Nutr. 44, 479-488.   DOI
6 Madara, J. L., C. Parkos, S. Colgan, A. Nusrat, K. Atisook, and P. Koustzani. 1992. The movement of solutes and cells across tight junctions. Ann. NY Acad. Sci. 664, 47-60.   DOI
7 Martinez, P. A. 1970. Ultrastructural modifications of intercellular junctions between tumor cells. Lab. Invest. 22, 605-614.
8 McCartney, M. D. and C. D. Cantu. 1992. Rabbit corneal epithelial wound repair: tight junction reformation. Curr. Eye Res. 11, 15-24.   DOI
9 Morita, K., M. Furuse, K. Fujimoto, and S. Tsukita. 1996. Claudin multigene family encoding fourtransmembrane domain protein components of tight junction strands. Proc. Natl. Acad. Sci. USA 96, 511-516.   DOI
10 Mullin, J. M. 1997. Potential interplay between luminal growth factors and increased tight junction permeability in epithelial carcinogenesis. J. Exp. Zool. 279, 484-489.   DOI
11 Park, C., O. C. Gweon, Y. H. Choi, and J. I. Kim. 2009. Aged black garlic inhibits cyclooxygenase-2 expression and prostaglandin E2 production by phorbol 12-myristate-13-acetate through Inactivation of nuclear factor-$\kappa$B. Cancer Prev. Res. 14, 161-170.
12 Tak, P. P. and B. Bresnihan. 2000. The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis. Arthritis Rheum. 43, 2619-2633.   DOI
13 Schneeberger, E. E. and R. D. Lynch. 2004. The tight junction: a multifunctional complex. Am. J. Physiol. Cell Physiol. 286, C1213-C1228.   DOI   ScienceOn
14 Shin, D. Y., M. K. Yoon, Y. W. Choi, O. C. Gweon, J. I. Kim, and Y. H. Choi. 2009. Apoptosis induction by aged black garlic extracts in AGS human gastric carcinoma cells. Cancer Prev. Res. 14, in press.
15 Swift, J. G., T. M. Mukherjee, and R. Rowland. 1983. Intercellular junctions in hepatocellular carcinoma. J. Submicrosc. Cytol. 15, 799-810.
16 Tunggal, J. A., I. Helfrich, A. Schmitz, H. Schwarz, D. Günzel, M. Fromm, R. Kemler, T. Krieg, and C. M. Niessen. 2005. E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J. 24, 1146-1156.   DOI
17 Van Itallie, C. M. and J. M. Anderson. 2004. The molecular physiology of tight junction pores. Physiol. 19, 331-338.   DOI
18 Wong, A. S. and B. M. Gumbiner. 2003. Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin. J. Cell Biol. 161, 1191-1203.   DOI
19 Chauhan, N. B. 2006. Effect of aged garlic extract on APP processing and tau phosphorylation in Alzheimer's transgenic model Tg2576. J. Ethnopharmacol. 108, 385-394.   DOI
20 Consolo, M., A. Amoroso, D. A. Spandidos, and M. C. Mazzarino. 2009. Matrix metalloproteinases and their inhibitors as markers of inflammation and fibrosis in chronic liver disease. Int. J. Mol. Med. 24, 143-152.
21 Katoh, M. 2005. Epithelial-mesenchymal transition in gastric cancer. Int. J. Oncol. 27, 1677-1683.
22 Birkedal-Hansen, H., W. G. Moore, M. K. Bodden, L. J. Windsor, B. Birkedal-Hansen, A. DeCarlo, and J. A. Engler. 1993. Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4, 197-250.
23 Ahmad, M. S., M. Pischetsrieder, and N. Ahmed. 2007. Aged garlic extract and S-allyl cysteine prevent formation of advanced glycation endproducts. Eur. J. Pharmaco. 561, 32-38.   DOI
24 Allison, G. L., G. M. Lowe, and K. Rahman. 2006. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J. Nutr. 136, 782S-788S.
25 Ariga, T. and T. Seki. 2006. Antithrombotic and anticancer effects of garlic-derived sulfur compounds: a review. Biofactors 26, 93-103.   DOI
26 Chandler, S., K. M. Miller, J. M. Clements, J. Lury, D. Corkill, D. C. Anthony, S. E. Adams, and A. J. Gearing. 1997. Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview. J. Neuroimmunol. 72, 155-161.   DOI