Asian Pacific Journal of Cancer Prevention

Asian Pacific Organization for Cancer Prevention (아시아태평양암예방학회)
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Tumorigenic Effects of Endocrine-disrupting Chemicals are Alleviated by Licorice (Glycyrrhiza glabra) Root Extract through Suppression of AhR Expression in Mammalian Cells

  • Chu, Xiao Ting (Department of Animal Biotechnology, Hankyong National University) ;
  • de la Cruz, Joseph (Department of Animal Life and Environmental Science, Hankyong National University) ;
  • Hwang, Seong Gu (Department of Animal Life and Environmental Science, Hankyong National University) ;
  • Hong, Heeok (Department of Medical Science, School of Medicine, Konkuk University)
  • Published : 2014.06.30

Abstract

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

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References

  1. Levine AJ (1997). p53, the cellular gatekeeper for growth and division. Cell, 88, 323-31. https://doi.org/10.1016/S0092-8674(00)81871-1
  2. Wahl GM, Carr AM (2001). The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat Cell Biol, 3, 277-86. https://doi.org/10.1038/ncb1201-e277
  3. Warner M, Eskenazi B, Mocarelli P, et al (2002). Serum dioxin concentrations and breast cancer risk in the seveso women's health study. Environ Health Perspect, 110, 625-8.
  4. Kamei J, Nakamura R, Ichiki H, Kubo M (2003). Anti-tussive principles of glycyrrhiza radix, a main component of the kampo preparations bakumondo-to (Mai-men-dong-tang). Eur J Pharmacol, 469, 159-63. https://doi.org/10.1016/S0014-2999(03)01728-X
  5. Kang JS, Yoon YD, Cho IJ, et al (2005). Glabridin, an isoflavan from licorice root, inhibits inducible nitric-oxide synthase expression and improves survival of mice in experimental model of septic shock. J Pharmacol Exp Ther, 312, 1187-94.
  6. Kerdivel G, Habauzit D, Pakdel F (2013). Assessment and molecular actions of endocrine-disrupting chemicals that interfere with estrogen receptor pathways. Int J Endocrinol, 2013, 501851.
  7. Mimuraa J, Fujii-Kuriyama Y (2003). Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta, 1619, 263-8. https://doi.org/10.1016/S0304-4165(02)00485-3
  8. Pelekanou V, Leclercq G (2011). Recent insights into the effect of natural and environmental estrogens on mammary development and carcinogenesis. Int J Dev Biol, 55, 869-78. https://doi.org/10.1387/ijdb.113369vp
  9. Polyak K, Lee MH, Erdjument-Bromage H, et al (1994). Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell, 78, 59-66. https://doi.org/10.1016/0092-8674(94)90572-X
  10. Read AP, Strachan T (1999). Human molecular genetics 2. New York: Wiley; ISBN 0-471-33061-2. Chapter 18: cancer Genetics.
  11. Ryan KM, Phillips AC, Vousden KH (2001). Regulation and function of the p53 tumor suppressor protein. Curr Opin Cell Biol, 13, 332-7. https://doi.org/10.1016/S0955-0674(00)00216-7
  12. Shanle EK, Xu W (2011). Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem Res Toxicol, 24, 6-19. https://doi.org/10.1021/tx100231n
  13. Craig WJ (1999). Health-promoting properties of common herbs. Am J Clin Nutr, 70, 491-9. https://doi.org/10.1093/ajcn/70.3.491s
  14. Cheel J, Antwerpen PV, Tumova L, et al (2010). Free radicalscavenging, antioxidant and immunostimulating effects of a licorice infusion (Glycyrrhiza glabra L). Food Chemistry, 122, 508-17. https://doi.org/10.1016/j.foodchem.2010.02.060
  15. Chen JX, Cheng MC, Li Y, Jiang CB (2011). Relationship between CYP1A1 genetic polymorphisms and renal cancer in China. Asian Pac J Cancer Prev, 12, 2163-6.
  16. Chen YJ, Hung CM, Kay N, et al (2012). Progesterone receptor is involved in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-stimulated breast cancer cells proliferation. Cancer Letter, 319, 223-31. https://doi.org/10.1016/j.canlet.2012.01.017
  17. Cravedi JP, Zalko D, Savouret JF, et al (2007). The concept of endocrine disruption and human health. Med Sci, 23, 198-204.
  18. Fukai T, Satoh K, Nomura T, Sakagami H (2003). Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra. Fitoterapia, 74, 624-9. https://doi.org/10.1016/S0367-326X(03)00164-3
  19. Giordano A, Normanno N (2009). Breast cancer in the postgenomic era. Brit J Cancer, 103, 155.
  20. Hrabia A, Lesniak A, Sechman A (2013). In vitro effects of TCDD, PCB126 and PCB153 on estrogen receptors, caspases and metalloproteinase-2 mRNA expression in the chicken shell gland. Folia Biologica, 61, 277-82. https://doi.org/10.3409/fb61_3-4.277
  21. Hu X, Moscinski LC (2011). CDC2: a monopotent or pluripotent CDK? Cell Prolif, 44, 205-11. https://doi.org/10.1111/j.1365-2184.2011.00753.x
  22. Jablonska O, Piasecka J, Petroff BK, et al (2011). In vitro effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on ovarian, pituitary and pineal function in pigs. Theriogenology, 76, 921-32. https://doi.org/10.1016/j.theriogenology.2011.04.023
  23. Beischlag TV, Morales JL, Hollingshead BD, Perdew GH (2008). The aryl hydrocarbon receptor complex and the control of gene expression. Toxicology, 268, 132-8.
  24. Abdel-Rahim M, Smith R, Safe S (2003). Aryl hydrocarbon receptor gene silencing with small inhibitory rna differentially modulates Ah-responsiveness in MCF-7 and HepG2 cancer cells. Mol Pharmacol, 63, 1373-81. https://doi.org/10.1124/mol.63.6.1373
  25. Abdel-Rahman WM, Moustafa YM, Ahmed BO, Mostafa RM (2012). Endocrine disruptors and breast cancer risk - time to consider the environment. Asian Pac J Cancer Prev, 13, 5937-46. https://doi.org/10.7314/APJCP.2012.13.12.5937
  26. Androutsopoulos VP, Tsatsakis AM, Spandidos DA (2009). Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer, 9, 187. https://doi.org/10.1186/1471-2407-9-187
  27. Bidgoli SA, Khorasani H, Keihan H, Sadeghipour A, Mehdizadeh A (2012). Role of endocrine disrupting chemicals in the occurrence of benign uterine leiomyomata: special emphasis on AhR tissue levels. Asian Pac J Cancer Prev, 11, 5445-50. https://doi.org/10.7314/APJCP.2012.13.11.5445
  28. Bidgoli SA, Korani M, Bozorgi N, et al (2011). Association between glycodelin and aryl hydrocarbon receptor in Iranian breast cancer patients: impact of environmental endocrine disrupting chemicals. Asian Pac J Cancer Prev, 12, 2431-5.
  29. Casalini P, Iorio MV, Berno V, et al (2007). Relationship between p53 and p27 expression following HER2 signaling. The Breast, 16, 597-605. https://doi.org/10.1016/j.breast.2007.05.007

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