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http://dx.doi.org/10.4162/nrp.2014.8.3.257

Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root  

Park, So Young (Department of Food Science and Nutrition, Hallym University)
Kim, Eun Ji (Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University)
Choi, Hyun Ju (Department of Food Science and Nutrition, Hallym University)
Seon, Mi Ra (Department of Food Science and Nutrition, Hallym University)
Lim, Soon Sung (Department of Food Science and Nutrition, Hallym University)
Kang, Young-Hee (Department of Food Science and Nutrition, Hallym University)
Choi, Myung-Sook (Center for Food and Nutritional Genomics Research and Department of Food Science and Nutrition, Kyungpook National University)
Lee, Ki Won (Advanced Institutes of Convergence Technology, Seoul National University)
Yoon Park, Jung Han (Department of Food Science and Nutrition, Hallym University)
Publication Information
Nutrition Research and Practice / v.8, no.3, 2014 , pp. 257-266 More about this Journal
Abstract
BACKGROUND/OBJECTIVE: Licorice has been shown to possess cancer chemopreventive effects. However, glycyrrhizin, a major component in licorice, was found to interfere with steroid metabolism and cause edema and hypertension. The roasting process of licorice modifies the chemical composition and converts glycyrrhizin to glycyrrhetinic acid. The purpose of this study was to examine the anti-carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to identify the active compound in EERL. MATERIALS/METHODS: Ethanol and aqueous extracts of roasted and un-roasted licorice were prepared. The active fraction was separated from the methylene chloride (MC)-soluble fraction of EERL and the structure of the purified compound was determined by nuclear magnetic resonance spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage skin carcinogenesis model. RESULTS: EERL was determined to be more potent and efficacious than the ethanol extract of un-roasted licorice in inhibiting the growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer cells. The aqueous extracts of un-roasted and roasted licorice showed minimal effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231 breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction and identified as the active compound of EERL. Both EERL and licochalcone A induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin papilloma formation in mice. CONCLUSIONS: Non-polar compounds in EERL exert potent anti-carcinogenic effects, and that roasted rather than un-roasted licorice should be favored as a cancer preventive agent, whether being used as an additive to food or medicine preparations.
Keywords
Roasted licorice roots; apoptosis; licochalcone A; cancer;
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1 Ouedraogo M, Charles C, Ouedraogo M, Guissou IP, Stevigny C, Duez P. An overview of cancer chemopreventive potential and safety of proanthocyanidins. Nutr Cancer 2011;63:1163-73.   DOI
2 Kinghorn AD, Chai HB, Sung CK, Keller WJ. The classical drug discovery approach to defining bioactive constituents of botanicals. Fitoterapia 2011;82:71-9.   DOI   ScienceOn
3 Tan AC, Konczak I, Sze DM, Ramzan I. Molecular pathways for cancer chemoprevention by dietary phytochemicals. Nutr Cancer 2011;63: 495-505.   DOI   ScienceOn
4 Vermeulen K, Van Bockstaele DR, Berneman ZN. Apoptosis: mechanisms and relevance in cancer. Ann Hematol 2005;84:627-39.   DOI   ScienceOn
5 Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer 2001;39:1-11.   DOI   ScienceOn
6 Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res 2008;22: 709-24.   DOI   ScienceOn
7 Yasue H, Itoh T, Mizuno Y, Harada E. Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice. Intern Med 2007;46:575-8.   DOI
8 van Uum SH. Liquorice and hypertension. Neth J Med 2005;63: 119-20.
9 Leitolf H, Dixit KC, Higham CE, Brabant G. Licorice - or more? Exp Clin Endocrinol Diabetes 2010;118:250-3.   DOI   ScienceOn
10 Omar HR, Komarova I, El-Ghonemi M, Fathy A, Rashad R, Abdelmalak HD, Yerramadha MR, Ali Y, Helal E, Camporesi EM. Licorice abuse: time to send a warning message. Ther Adv Endocrinol Metab 2012;3:125-38.   DOI   ScienceOn
11 Murphy SC, Agger S, Rainey PM. Too much of a good thing: a woman with hypertension and hypokalemia. Clin Chem 2009;55: 2093-6.
12 Sung MW, Li PC. Chemical analysis of raw, dry-roasted, and honeyroasted licorice by capillary electrophoresis. Electrophoresis 2004;25: 3434-40.   DOI   ScienceOn
13 Hwang IK, Lim SS, Choi KH, Yoo KY, Shin HK, Kim EJ, Yoon-Park JH, Kang TC, Kim YS, Kwon DY, Kim DW, Moon WK, Won MH. Neuroprotective effects of roasted licorice, not raw form, on neuronal injury in gerbil hippocampus after transient forebrain ischemia. Acta Pharmacol Sin 2006;27:959-65.   DOI   ScienceOn
14 Majima T, Yamada T, Tega E, Sakurai H, Saiki I, Tani T. Pharmaceutical evaluation of liquorice before and after roasting in mice. J Pharm Pharmacol 2004;56:589-95.   DOI   ScienceOn
15 Wang B, Zou K, Yang XB, He WY, Zhao YY, Zhang RY. Two new flavanone glycosides from Glycyrrhizia inflata. Yao Xue Xue Bao 1997;32:199-202.
16 Kim KR, Jeong CK, Park KK, Choi JH, Park JH, Lim SS, Chung WY. Anti-inflammatory effects of licorice and roasted licorice extracts on TPA-induced acute inflammation and collagen-induced arthritis in mice. J Biomed Biotechnol 2010;2010:709378.
17 Cho HJ, Kim WK, Kim EJ, Jung KC, Park S, Lee HS, Tyner AL, Park JH. Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. Am J Physiol Gastrointest Liver Physiol 2003;284:G996-1005.   DOI   ScienceOn
18 Eguchi Y, Srinivasan A, Tomaselli KJ, Shimizu S, Tsujimoto Y. ATPdependent steps in apoptotic signal transduction. Cancer Res 1999; 59:2174-81.
19 Yo YT, Shieh GS, Hsu KF, Wu CL, Shiau AL. Licorice and licochalcone- a induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway. J Agric Food Chem 2009;57:8266-73.   DOI   ScienceOn
20 Mumoli N, Cei M. Licorice-induced hypokalemia. Int J Cardiol 2008;124:e42-4.   DOI   ScienceOn
21 Sontia B, Mooney J, Gaudet L, Touyz RM. Pseudohyperaldosteronism, liquorice, and hypertension. J Clin Hypertens (Greenwich) 2008;10:153-7.   DOI   ScienceOn
22 Kim JK, Oh SM, Kwon HS, Oh YS, Lim SS, Shin HK. Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages. Biochem Biophys Res Commun 2006;345:1215-23.   DOI   ScienceOn
23 Kim JK, Shin EK, Park JH, Kim YH, Park JH. Antitumor and antimetastatic effects of licochalcone A in mouse models. J Mol Med (Berl) 2010;88:829-38.   DOI   ScienceOn
24 Li J, Lee YS, Choi JS, Sung HY, Kim JK, Lim SS, Kang YH. Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking Akt activation and TGFbeta signaling. Phytomedicine 2010;17:800-10.   DOI   ScienceOn
25 Kim YH, Shin EK, Kim DH, Lee HH, Park JH, Kim JK. Antiangiogenic effect of licochalcone A. Biochem Pharmacol 2010;80:1152-9.   DOI   ScienceOn
26 Lee CK, Son SH, Park KK, Park JH, Lim SS, Kim SH, Chung WY. Licochalcone A inhibits the growth of colon carcinoma and attenuates cisplatin-induced toxicity without a loss of chemotherapeutic efficacy in mice. Basic Clin Pharmacol Toxicol 2008;103:48-54.   DOI   ScienceOn
27 Jo EH, Kim SH, Ra JC, Kim SR, Cho SD, Jung JW, Yang SR, Park JS, Hwang JW, Aruoma OI, Kim TY, Lee YS, Kang KS. Chemopreventive properties of the ethanol extract of chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. Cancer Lett 2005;230: 239-47.   DOI   ScienceOn
28 Seon MR, Park SY, Kwon SJ, Lim SS, Choi HJ, Park H, Lim do Y, Kim JS, Lee CH, Kim J, Park JH. Hexane/ethanol extract of Glycyrrhiza uralensis and its active compound isoangustone A induce G1 cycle arrest in DU145 human prostate and 4T1 murine mammary cancer cells. J Nutr Biochem 2012;23:85-92.   DOI   ScienceOn
29 Rafi MM, Vastano BC, Zhu N, Ho CT, Ghai G, Rosen RT, Gallo MA, DiPaola RS. Novel polyphenol molecule isolated from licorice root (Glycrrhiza glabra) induces apoptosis, G2/M cell cycle arrest, and Bcl-2 phosphorylation in tumor cell lines. J Agric Food Chem 2002;50:677-84.   DOI   ScienceOn
30 Szliszka E, Czuba ZP, Mazur B, Sedek L, Paradysz A, Krol W. Chalcones enhance TRAIL-induced apoptosis in prostate cancer cells. Int J Mol Sci 2009;11:1-13.   DOI   ScienceOn
31 Fu Y, Hsieh TC, Guo J, Kunicki J, Lee MY, Darzynkiewicz Z, Wu JM. Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgenindependent PC-3 prostate cancer cells. Biochem Biophys Res Commun 2004;322:263-70.   DOI   ScienceOn
32 Martinou JC, Green DR. Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2001;2:63-7.
33 Green DR, Reed JC. Mitochondria and apoptosis. Science 1998;281: 1309-12.   DOI   ScienceOn
34 Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 1999;15:269-90.   DOI   ScienceOn
35 Plati J, Bucur O, Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb) 2011;3:279-96.   DOI   ScienceOn
36 Ho PK, Hawkins CJ. Mammalian initiator apoptotic caspases. FEBS J 2005;272:5436-53.   DOI   ScienceOn
37 Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13:1899-911.   DOI   ScienceOn
38 Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011;30:87.   DOI
39 Lee SK, Park KK, Park JH, Lim SS, Chung WY. The inhibitory effect of roasted licorice extract on human metastatic breast cancer cell-induced bone destruction. Phytother Res 2013;27:1776-83.   DOI   ScienceOn
40 Jung JI, Lim SS, Choi HJ, Cho HJ, Shin HK, Kim EJ, Chung WY, Park KK, Park JH. Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells. J Nutr Biochem 2006;17:689-96.   DOI   ScienceOn
41 Choi HJ, Seon MR, Lim SS, Kim JS, Chun HS, Park JH. Hexane/ethanol extract of Glycyrrhiza uralensis licorice suppresses doxorubicininduced apoptosis in H9c2 rat cardiac myoblasts. Exp Biol Med (Maywood) 2008;233:1554-60.   DOI   ScienceOn
42 Jo EH, Hong HD, Ahn NC, Jung JW, Yang SR, Park JS, Kim SH, Lee YS, Kang KS. Modulations of the Bcl-2/Bax family were involved in the chemopreventive effects of licorice root (Glycyrrhiza uralensis Fisch) in MCF-7 human breast cancer cell. J Agric Food Chem 2004;52:1715-9.   DOI   ScienceOn