Synergetic downregulation of 67 kDa laminin receptor by the green tea (Camellia sinensis) secondary plant compound epigallocatechin gallate: a new gateway in metastasis prevention?

BMC Complementary and Alternative Medicine

Michael W Pfaffl¹  Jakob Müller¹ 

[1] Physiology Weihenstephan, Technische Universität München, Research Center for Nutrition and Food Science, Weihenstephaner Berg 3, 85350 Freising, Germany

关键词: RNA interference;    miRNA;    IPEC-J2;    EGCG;    Cancer;   

Others  :  1231367
DOI  :  10.1186/1472-6882-12-258

 received in 2012-06-12, accepted in 2012-12-14,  发布年份 2012

【 摘 要 】

Background

In traditional Chinese medicine, green tea is considered to have a life-prolonging effect, possibly as a result of its rich content of antioxidant tea polyphenols, and hence has the potential to prevent cancer. This study investigated the role of the major tea secondary plant compound epigallocatechin gallate (EGCG) for its inhibitory effects on the metastasis-associated 67 kDa laminin receptor (67LR).

Methods

To clarify the impact of EGCG on siRNA-silenced expression of 67LR, we applied an adenoviral-based intestinal in vitro knockdown model, porcine IPEC-J2 cells. Quantitative real-time polymerase chain reaction was performed to analyze 67LR gene expression following treatment with physiological and pharmacological concentrations of EGCG (1.0 g/l, 0.1 g/l, 0.02 g/l and 0.002 g/l).

Results

We report co-regulation of EGCG and 67LR, which is known to be an EGCG receptor. siRNA selectively and highly significantly suppressed expression of 67LR under the impact of EGCG in a synergetic manner.

Conclusions

Our findings suggest that 67LR expression is regulated by EGCG via a negative feedback loop. The explicit occurrence of this effect in synergy with a small RNA pathway and a plant-derived drug reveals a new mode of action. Our findings may help to provide insights into the many unsolved health-promoting activities of other natural pharmaceuticals.

【 授权许可】

   
2012 Müller and Pfaffl; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Sang S, Lambert JD, Ho CT, Yang CS: The chemistry and biotransformation of tea constituents. Pharmacol Res 2011, 64(2):87-99.
• [2]Yang CS, Wang H, Li GX, Yang Z, Guan F, Jin H: Cancer prevention by tea: Evidence from laboratory studies. Pharmacol Res 2011, 64(2):113-122.
• [3]Donaldson MS: Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr J 2004, 3:19. BioMed Central Full Text
• [4]Shankar S, Ganapathy S, Srivastava RK: Green tea polyphenols: biology and therapeutic implications in cancer. Front Biosci 2007, 12:4881-4899.
• [5]Yuan JM, Sun C, Butler LM: Tea and cancer prevention: epidemiological studies. Pharmacol Res 2011, 64(2):123-135.
• [6]Beltz LA, Bayer DK, Moss AL, Simet IM: Mechanisms of cancer prevention by green and black tea polyphenols. Anticancer Agents Med Chem 2006, 6(5):389-406.
• [7]Kazi A, Smith DM, Daniel K, Zhong S, Gupta P, Bosley ME, Dou QP: Potential molecular targets of tea polyphenols in human tumor cells: significance in cancer prevention. In Vivo 2002, 16(6):397-403.
• [8]Park AM, Dong Z: Signal transduction pathways: targets for green and black tea polyphenols. J Biochem Mol Biol 2003, 36(1):66-77.
• [9]Tachibana H, Koga K, Fujimura Y, Yamada K: A receptor for green tea polyphenol EGCG. Nat Struct Mol Biol 2004, 11(4):380-381.
• [10]Umeda D, Yano S, Yamada K, Tachibana H: Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor. J Biol Chem 2008, 283(6):3050-3058.
• [11]Montuori N, Sobel ME: The 67-kDa laminin receptor and tumor progression. Curr Top Microbiol Immunol 1996, 213(Pt 1):205-214.
• [12]Hand PH, Thor A, Schlom J, Rao CN, Liotta L: Expression of laminin receptor in normal and carcinomatous human tissues as defined by a monoclonal antibody. Cancer Res 1985, 45(6):2713-2719.
• [13]Malinoff HL, Wicha MS: Isolation of a cell surface receptor protein for laminin from murine fibrosarcoma cells. J Cell Biol 1983, 96(5):1475-1479.
• [14]Sobel ME: Differential expression of the 67 kDa laminin receptor in cancer. Semin Cancer Biol 1993, 4(5):311-317.
• [15]Terranova VP, Rao CN, Kalebic T, Margulies IM, Liotta LA: Laminin receptor on human breast carcinoma cells. Proc Natl Acad Sci U S A 1983, 80(2):444-448.
• [16]Liotta LA: Tumor invasion and metastases - role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res 1986, 46(1):1-7.
• [17]Nelson J, McFerran NV, Pivato G, Chambers E, Doherty C, Steele D, Timson DJ: The 67 kDa laminin receptor: structure, function and role in disease. Biosci Rep 2008, 28(1):33-48.
• [18]Berno V, Porrini D, Castiglioni F, Campiglio M, Casalini P, Pupa SM, Balsari A, Menard S, Tagliabue E: The 67 kDa laminin receptor increases tumor aggressiveness by remodeling laminin-1. Endocr Relat Cancer 2005, 12(2):393-406.
• [19]Iwamoto Y, Robey FA, Graf J, Sasaki M, Kleinman HK, Yamada Y, Martin GR: YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science 1987, 238(4830):1132-1134.
• [20]Chen FX, Qian YR, Duan YH, Ren WW, Yang Y, Zhang CC, Qiu YM, Ji YH: Down-regulation of 67LR reduces the migratory activity of human glioma cells in vitro. Brain Res Bull 2009, 79(6):402-408.
• [21]Schierack P, Nordhoff M, Pollmann M, Weyrauch KD, Amasheh S, Lodemann U, Jores J, Tachu B, Kleta S, Blikslager A, et al.: Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine. Histochem Cell Biol 2006, 125(3):293-305.
• [22]Müller J, Thirion C, Pfaffl MW: Electric cell-substrate impedance sensing (ECIS) based real-time measurement of titer dependent cytotoxicity induced by adenoviral vectors in an IPI-2I cell culture model. Biosens Bioelectron 2011, 26(5):2000-2005.
• [23]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 2001, 25(4):402-408.
• [24]Freeman WM, Walker SJ, Vrana KE: Quantitative RT-PCR: pitfalls and potential. Biotechniques 1999, 26(1):112-122. 124–115
• [25]Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, et al.: The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 2009, 55(4):611-622.
• [26]Bergkvist A, Rusnakova V, Sindelka R, Garda JM, Sjogreen B, Lindh D, Forootan A, Kubista M: Gene expression profiling - Clusters of possibilities. Methods 2010, 50(4):323-335.
• [27]Jolliffe IT: Introduction, Principal Component Analysis. New York: Springer; 2002:1-9.
• [28]Finnegan EJ, Matzke MA: The small RNA world. J Cell Sci 2003, 116(Pt 23):4689-4693.
• [29]Fang Z, Rajewsky N: The impact of miRNA target sites in coding sequences and in 3′UTRs. PLoS One 2011, 6(3):e18067.
• [30]Aigner A: MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl) 2011, 89(5):445-457.
• [31]Wewer UM, Liotta LA, Jaye M, Ricca GA, Drohan WN, Claysmith AP, Rao CN, Wirth P, Coligan JE, Albrechtsen R, et al.: Altered levels of laminin receptor mRNA in various human carcinoma cells that have different abilities to bind laminin. Proc Natl Acad Sci U S A 1986, 83(19):7137-7141.
• [32]Rao M, Manishen WJ, Maheshwari Y, Sykes DE, Siyanova EY, Tyner AL, Weiser MM: Laminin receptor expression in rat intestine and liver during development and differentiation. Gastroenterology 1994, 107(3):764-772.