Planta Med 2013; 79(17): 1648-1652
DOI: 10.1055/s-0033-1351020
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Inhibition of β-Catenin Signaling Involved in the Biological Activities of a Lignan E2S Isolated from Carya cathayensis Fruits

Xichun Xia
1   College of Life Science, Liaoning University, Shenyang, Peopleʼs Republic of China
,
Xiuli Bi
1   College of Life Science, Liaoning University, Shenyang, Peopleʼs Republic of China
,
Wei Wu
2   Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Yanhua Mou
2   Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Yue Hou
2   Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Kaiqing Zhang
1   College of Life Science, Liaoning University, Shenyang, Peopleʼs Republic of China
,
Yuqing Zhao
2   Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 29. Juli 2013
revised 06. September 2013

accepted 30. September 2013

Publikationsdatum:
11. November 2013 (online)

Abstract

Carya cathayensis is a fruit-bearing plant that belongs to the Juglandaceae family and is widely distributed throughout the world. It possesses various important biological activities. We have previously isolated an antitumor compound from the shell of C. cathayensis fruits and named it E2S ((E)-3-[(2S,3R)-2,3-dihydro-2-(4′-hydroxy-3′-methoxyphenyl)-3-hydroxymethyl-7-methoxy-1-benzo[b]furan-5-yl]-2-propenal). In this study, we investigated the antitumor activity of E2S against various human colorectal cancer cell lines (HCT116, HT29, SW480, LoVo). The results showed that E2S could significantly inhibit the growth of cancer cells in a dose-dependent manner, as well as disrupt the progression of the cell cycle. Mechanistic study revealed that E2S could decrease the protein levels of β-catenin and its downstream targets (such as c-myc, a key transcriptional target of β-catenin) in the cells. In addition, it also significantly suppressed β-catenin/TCF transcriptional activity. Taken together, the results suggested that E2S might partially exert an antiproliferative effect on human colorectal cancer cells by targeting β-catenin signaling, a finding that might potentially translate into a chemotherapeutic strategy for the treatment of cancer. It might also have implications for cancer prevention strategies.

 
  • References

  • 1 Kelloff GJ, Lippman SM, Dannenberg AJ, Sigman CC, Pearce HL, Reid BJ, Szabo E, Jordan VC, Spitz MR, Mills GB, Papadimitrakopoulou VA, Lotan R, Aggarwal BB, Bresalier RS, Kim J, Arun B, Lu KH, Thomas ME, Rhodes HE, Brewer MA, Follen M, Shin DM, Parnes HL, Siegfried JM, Evans AA, Blot WJ, Chow WH, Blount PL, Maley CC, Wang KK, Lam S, Lee JJ, Dubinett SM, Engstrom PF, Meyskens jr. FL, OʼShaughnessy J, Hawk ET, Levin B, Nelson WG, Hong WK. Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer – a plan to move forward. Clin Cancer Res 2006; 12: 3661-3697
  • 2 Mazieres J, He B, You L, Xu Z, Jablons DM. Wnt signaling in lung cancer. Cancer Lett 2005; 222: 1-10
  • 3 Turashvili G, Bouchal J, Burkadze G, Kolar Z. Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology 2006; 73: 213-223
  • 4 Lee HC, Kim M, Wands JR. Wnt/Frizzled signaling in hepatocellular carcinoma. Front Biosci 2006; 11: 1901-1915
  • 5 Terry S, Yang X, Chen MW, Vacherot F, Buttyan R. Multifaceted interaction between the androgen and Wnt signaling pathways and the implication for prostate cancer. J Cell Biochem 2006; 99: 402-410
  • 6 Clement G, Jablons DM, Benhattar J. Targeting the Wnt signaling pathway to treat Barrettʼs esophagus. Expert Opin Ther Targets 2007; 11: 375-389
  • 7 Herbst A, Kolligs FT. Wnt signaling as a therapeutic target for cancer. Methods Mol Biol 2007; 361: 63-91
  • 8 Luo J, Chen J, Deng ZL, Luo X, Song WX, Sharff KA, Tang N, Haydon RC, Luu HH, He TC. Wnt signaling and human diseases: what are the therapeutic implications?. Lab Invest 2007; 87: 97-103
  • 9 Kim SH, Lee KS, Son JK, Je GH, Lee JS, Lee CH, Cheong CJ. Cytotoxic compounds from the roots of Juglans mandshurica . J Nat Prod 1998; 61: 643-645
  • 10 Cortes B, Nunez I, Cofan M, Gilabert R, Perez-Heras A, Casals E, Deulofeu R, Ros E. Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J Am Coll Cardiol 2006; 48: 1666-1671
  • 11 Griel AE, Kris-Etherton PM. Tree nuts and the lipid profile: a review of clinical studies. Br J Nutr 2006; 96: 68-78
  • 12 Ryan E, Galvin K, OʼConnor TP, Maguire AR, OʼBrien NM. Fatty acid profile, tocopherol, squalene and phytosterol content of brazil, pecan, pine, pistachio and cashew nuts. Int J Food Sci Nutr 2006; 57: 219-228
  • 13 Erdemoglu N, Kupeli E, Yesilada E. Anti-inflammatory and antinociceptive activity assessment of plants used as remedy in Turkish folk medicine. J Ethnopharmacol 2003; 89: 123-129
  • 14 Wu W, Bi XL, Cao JQ, Zhang KQ, Zhao YQ. New antitumor compounds from Carya cathayensis . Bioorg Med Chem Lett 2012; 22: 1895-1898
  • 15 Orford K, Orford CC, Byers SW. Exogenous expression of beta-catenin regulates contact inhibition, anchorage-independent growth, anoikis, and radiation-induced cell cycle arrest. J Cell Biol 1999; 146: 855-868
  • 16 Tong C, Yin Z, Song Z, Dockendorff A, Huang C, Mariadason J, Flavell RA, Davis RJ, Augenlicht LH, Yang W. c-Jun NH2-terminal kinase 1 plays a critical role in intestinal homeostasis and tumor suppression. Am J Pathol 2007; 171: 297-303
  • 17 Hu D, Fang W, Han A, Gallagher L, Davis RJ, Xiong B, Yang W. c-Jun N-terminal kinase 1 interacts with and negatively regulates Wnt/beta-catenin signaling through GSK3beta pathway. Carcinogenesis 2008; 29: 2317-2324
  • 18 Hu D, Bi X, Fang W, Han A, Yang W. GSK3beta is involved in JNK2-mediated beta-catenin inhibition. PLoS One 2009; 4: e6640
  • 19 Kennedy NJ, Davis RJ. Role of JNK in tumor development. Cell Cycle 2003; 2: 199-201
  • 20 Potapova O, Gorospe M, Bost F, Dean NM, Gaarde WA, Mercola D, Holbrook NJ. c-Jun N-terminal kinase is essential for growth of human T98 G glioblastoma cells. J Biol Chem 2000; 275: 24767-24775
  • 21 Potapova O, Gorospe M, Dougherty RH, Dean NM, Gaarde WA, Holbrook NJ. Inhibition of c-Jun N-terminal kinase 2 expression suppresses growth and induces apoptosis of human tumor cells in a p 53-dependent manner. Mol Cell Biol 2000; 20: 1713-1722
  • 22 Bi X, Zhao Y, Fang W, Yang W. Anticancer activity of Panax notoginseng extract 20(S)-25-OCH3-PPD: Targeting beta-catenin signaling. Clin Exp Pharmacol Physiol 2009; 36: 1074-1078
  • 23 Yang AD, Fan F, Camp ER, van Buren G, Liu W, Somcio R, Gray MJ, Cheng H, Hoff PM, Ellis LM. Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res 2006; 12: 4147-4153