Chemopreventive Effects of Licorice and Its Components

详细信息    查看全文

• 作者：Ann M. Bode ; Zigang Dong
• 关键词：Glycyrrhizic acid ; Glycyrrhetic acid ; Iso ; liquiritigenin ; Isoangustone A ; Licochalcone A ; Licochalcone E
• 刊名：Current Pharmacology Reports
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：1
• 期：1
• 页码：60-71
• 全文大小：323KB
• 参考文献：Papers of particular interest, published recently, have been highlighted as: 鈥?Of importance,鈥⑩€?Of major importance1.Shibata S. A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice. Yakugaku Zasshi. 2000;120(10):849鈥?2.PubMed
  2.Gibson MR. Glycyrrhiza in old and new perspectives. Lloydia. 1978;41(4):348鈥?4.PubMed
  3.GRAS status of licorice (Glycyrrhiza), ammoniated glycyrrhizin, and monoammonium glycyrrhizinate, Fed Reg 50 (1985).
  4.Johns C. Glycyrrhizic acid toxicity caused by consumption of licorice candy cigars. Cjem. 2009;11(1):94鈥?.PubMed
  5.Spinks EA, Fenwick GR. The determination of glycyrrhizin in selected UK liquorice product. Food Addit Contam. 1990;7(6):769鈥?8.PubMed
  6.Ibsen KK. Liquorice consumption and its influence on blood pressure in Danish school-children. Dan Med Bull. 1981;28(3):124鈥?.PubMed
  7.Gomez-Sanchez EP, Gomez-Sanchez CE. Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Am J Physiol. 1992;263(6 Pt 1):E1125鈥?0.PubMed
  8.Sigurjonsdottir HA, Franzson L, Manhem K, Ragnarsson J, Sigurdsson G, Wallerstedt S. Liquorice-induced rise in blood pressure: a linear dose鈥搑esponse relationship. J Hum Hypertens. 2001;15(8):549鈥?2.PubMed
  9.Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T. Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci. 2002;71(12):1449鈥?3.PubMed
  10.Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer. 2001;39(1):1鈥?1.PubMed
  11.Fuhrman B, Volkova N, Kaplan M, Presser D, Attias J, Hayek T, et al. Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: increased resistance of LDL to atherogenic modifications, reduced plasma lipid levels, and decreased systolic blood pressure. Nutrition. 2002;18(3):268鈥?3.PubMed
  12.Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res. 2008;22(6):709鈥?4.PubMed
  13.Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. 2007;20(5):308鈥?3.PubMed
  14.Kusano A, Nikaido T, Kuge T, Ohmoto T, Delle Monache G, Botta B, et al. Inhibition of adenosine 3鈥?5鈥?cyclic monophosphate phosphodiesterase by flavonoids from licorice roots and 4-arylcoumarins. Chem Pharm Bull. 1991;39(4):930鈥?.PubMed
  15.Vaya J, Belinky PA, Aviram M. Antioxidant constituents from licorice roots: isolation, structure elucidation and antioxidative capacity toward LDL oxidation. Free Radic Biol Med. 1997;23(2):302鈥?3.PubMed
  16.Hatano T, Shintani Y, Aga Y, Shiota S, Tsuchiya T, Yoshida T. Phenolic constituents of licorice. VIII. Structures of glicophenone and glicoisoflavanone, and effects of licorice phenolics on methicillin-resistant Staphylococcus aureus. Chem Pharm Bull. 2000;48(9):1286鈥?2.PubMed
  17.Nomura T, Fukai T. Phenolic constituents of licorice (Glycyrrhiza species). Fortschr Chem Org Naturst. 1998;73:1鈥?58.PubMed
  18.Hattori M, Sakamoto T, Yamagishi T, Sakamoto K, Konishi K, Kobashi K, et al. Metabolism of glycyrrhizin by human intestinal flora. II. Isolation and characterization of human intestinal bacteria capable of metabolizing glycyrrhizin and related compounds. Chem Pharm Bull. 1985;33(1):210鈥?.PubMed
  19.Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CH, Edwards CR. Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet. 1987;2(8563):821鈥?.PubMed
  20.Whorwood CB, Sheppard MC, Stewart PM. Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology. 1993;132(6):2287鈥?2.PubMed
  21.van Rossum TG, Vulto AG, Hop WC, Brouwer JT, Niesters HG, Schalm SW. Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial. J Gastroenterol Hepatol. 1999;14(11):1093鈥?.PubMed
  22.Curreli F, Friedman-Kien AE, Flore O. Glycyrrhizic acid alters Kaposi sarcoma-associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes. J Clin Invest. 2005;115(3):642鈥?2.PubMed Central PubMed
  23.Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361(9374):2045鈥?.PubMed
  24.Hoever G, Baltina L, Michaelis M, Kondratenko R, Tolstikov GA, Doerr HW, et al. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. J Med Chem. 2005;48(4):1256鈥?.PubMed
  25.Lee CH, Park SW, Kim YS, Kang SS, Kim JA, Lee SH, et al. Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull. 2007;30(10):1898鈥?04.PubMed
  26.Abe M, Akbar F, Hasebe A, Horiike N, Onji M. Glycyrrhizin enhances interleukin-10 production by liver dendritic cells in mice with hepatitis. J Gastroenterol. 2003;38(10):962鈥?.PubMed
  27.Gumpricht E, Dahl R, Devereaux MW, Sokol RJ. Licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes. J Biol Chem. 2005;280(11):10556鈥?3.PubMed
  28.Shinada M, Azuma M, Kawai H, Sazaki K, Yoshida I, Yoshida T, et al. Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus. Proc Soc Exp Biol Med. 1986;181(2):205鈥?0.PubMed
  29.Cherng JM, Lin HJ, Hung MS, Lin YR, Chan MH, Lin JC. Inhibition of nuclear factor kappaB is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons. Eur J Pharmacol. 2006;547(1鈥?):10鈥?1.PubMed
  30.Agarwal R, Wang ZY, Mukhtar H. Inhibition of mouse skin tumor-initiating activity of DMBA by chronic oral feeding of glycyrrhizin in drinking water. Nutr Cancer. 1991;15(3鈥?):187鈥?3.PubMed
  31.Aydemir EA, Oz ES, Gokturk RS, Ozkan G, Fiskin K. Glycyrrhiza flavescens subsp. antalyensis exerts antiproliferative effects on melanoma cells via altering TNF-alpha and IFN-alpha levels. Food Chem Toxicol. 2011;49(4):820鈥?.PubMed
  32.Kobayashi M, Fujita K, Katakura T, Utsunomiya T, Pollard RB, Suzuki F. Inhibitory effect of glycyrrhizin on experimental pulmonary metastasis in mice inoculated with B16 melanoma. Anticancer Res. 2002;22(6C):4053鈥?.PubMed
  33.鈥?/div>Cherng JM, Tsai KD, Yu YW, Lin JC. Molecular mechanisms underlying chemopreventive activities of glycyrrhizic acid against UVB-radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis. Radiat Res. 2011;176(2):177鈥?6. PubMed PMID: 21545294. Epub 2011/05/07. Eng. This group showed that ingesting orally licorice compounds could prevent UVB induced skin cancer, making it more applicable to the human condition.
  34.Thirugnanam S, Xu L, Ramaswamy K, Gnanasekar M. Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. Oncol Rep. 2008;20(6):1387鈥?2.PubMed
  35.Hibasami H, Iwase H, Yoshioka K, Takahashi H. Glycyrrhizin induces apoptosis in human stomach cancer KATO III and human promyelotic leukemia HL-60 cells. Int J Mol Med. 2005;16(2):233鈥?.PubMed
  36.Hibasami H, Iwase H, Yoshioka K, Takahashi H. Glycyrrhetic acid (a metabolic substance and aglycon of glycyrrhizin) induces apoptosis in human hepatoma, promyelotic leukemia and stomach cancer cells. Int J Mol Med. 2006;17(2):215鈥?.PubMed
  37.Lin D, Zhong W, Li J, Zhang B, Song G, Hu T. Involvement of BID translocation in glycyrrhetinic acid and 11-deoxy glycyrrhetinic acid-induced attenuation of gastric cancer growth. Nutr Cancer. 2014;66(3):463鈥?3.PubMed
  38.Niwa K, Lian Z, Onogi K, Yun W, Tang L, Mori H, et al. Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice. Oncol Rep. 2007;17(3):617鈥?2.PubMed
  39.Wang D, Wong HK, Feng YB, Zhang ZJ. 18beta-glycyrrhetinic acid induces apoptosis in pituitary adenoma cells via ROS/MAPKs-mediated pathway. J Neurooncol. 2014;116(2):221鈥?0.PubMed
  40.Rossi T, Castelli M, Zandomeneghi G, Ruberto A, Benassi L, Magnoni C, et al. Selectivity of action of glycyrrhizin derivatives on the growth of MCF-7 and HEP-2 cells. Anticancer Res. 2003;23(5A):3813鈥?.PubMed
  41.Huang RY, Chu YL, Huang QC, Chen XM, Jiang ZB, Zhang X, et al. 18beta-Glycyrrhetinic acid suppresses cell proliferation through inhibiting thromboxane synthase in non-small cell lung cancer. PLoS ONE. 2014;9(4):e93690.PubMed Central PubMed
  42.Song J, Ko HS, Sohn EJ, Kim B, Kim JH, Kim HJ, et al. Inhibition of protein kinase C alpha/betaII and activation of c-Jun NH2-terminal kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung cancer NCI-H460 cells. Bioorg Med Chem Lett. 2014;24(4):1188鈥?1.PubMed
  43.Khan R, Khan AQ, Lateef A, Rehman MU, Tahir M, Ali F, et al. Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats. PLoS ONE. 2013;8(2):e56020.PubMed Central PubMed
  44.Chueh FS, Hsiao YT, Chang SJ, Wu PP, Yang JS, Lin JJ, et al. Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase- and mitochondria-dependent pathways. Oncol Rep. 2012;28(6):2069鈥?6.PubMed
  45.Shintani S, Murase H, Tsukagoshi H, Shiigai T. Glycyrrhizin (licorice)-induced hypokalemic myopathy. Report of 2 cases and review of the literature. Eur Neurol. 1992;32(1):44鈥?1.PubMed
  46.Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc. 2003;78(6):767鈥?.PubMed
  47.Mumoli N, Cei M. Licorice-induced hypokalemia. Int J Cardiol. 2008;124(3):e42鈥?.PubMed
  48.Celik MM, Karakus A, Zeren C, Demir M, Bayarogullari H, Duru M, et al. Licorice induced hypokalemia, edema, and thrombocytopenia. Hum Exp Toxicol. 2012;31(12):1295鈥?.PubMed
  49.Final report on the safety assessment of glycyrrhetinic acid, potassium glycyrrhetinate, disodium succinoyl glycyrrhetinate, glyceryl glycyrrhetinate, glycyrrhetinyl stearate, stearyl glycyrrhetinate, glycyrrhizic acid, ammonium glycyrrhizate, dipotassium glycyrrhizate, disodium glycyrrhizate, trisodium glycyrrhizate, methyl glycyrrhizate, and potassium glycyrrhizinate. Int J Toxicol. 2007;26 Suppl 2:79鈥?12. PubMed PMID: 17613133. Epub 2007/12/06. eng.
  50.Cuendet M, Guo J, Luo Y, Chen S, Oteham CP, Moon RC, et al. Cancer chemopreventive activity and metabolism of isoliquiritigenin, a compound found in licorice. Cancer Prev Res (Phila). 2010;3(2):221鈥?2.
  51.Ye L, Gho WM, Chan FL, Chen S, Leung LK. Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase. Int J Cancer. 2009;124(5):1028鈥?6.PubMed
  52.Vandooren J, Van den Steen PE, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Crit Rev Biochem Mol Biol. 2013;48(3):222鈥?2.PubMed
  53.Ma J, Zhang Q, Chen S, Fang B, Yang Q, Chen C, et al. Mitochondrial dysfunction promotes breast cancer cell migration and invasion through HIF1alpha accumulation via increased production of reactive oxygen species. PLoS ONE. 2013;8(7):e69485.PubMed Central PubMed
  54.Cao Y. VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs. Nat Rev Endocrinol. 2014;10(9):530鈥?.PubMed
  55.Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141(1):52鈥?7.PubMed Central PubMed
  56.Lorusso V, Marech I. Novel plant-derived target drugs: a step forward from licorice? Expert Opin Ther Targets. 2013;17(4):333鈥?.PubMed
  57.Kang SW, Choi JS, Choi YJ, Bae JY, Li J, Kim DS, et al. Licorice isoliquiritigenin dampens angiogenic activity via inhibition of MAPK-responsive signaling pathways leading to induction of matrix metalloproteinases. J Nutr Biochem. 2010;21(1):55鈥?5.PubMed
  58.Lau GT, Ye L, Leung LK. The licorice flavonoid isoliquiritigenin suppresses phorbol ester-induced cyclooxygenase-2 expression in the non-tumorigenic MCF-10A breast cell line. Planta Med. 2010;76(8):780鈥?.PubMed
  59.Takahashi T, Takasuka N, Iigo M, Baba M, Nishino H, Tsuda H, et al. Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci. 2004;95(5):448鈥?3.PubMed
  60.鈥?/div>Zhao H, Zhang X, Chen X, Li Y, Ke Z, Tang T, et al. Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6. Toxicol Appl Pharmacol. 2014;279(3):311鈥?1. PubMed PMID: 25026504. Epub 2014/07/16. Eng. Showed different, interesting mechanism for the anticancer activity of iso-liquiritigenin.
  61.Zhou Y, Ho WS. Combination of liquiritin, isoliquiritin and isoliquirigenin induce apoptotic cell death through upregulating p53 and p21 in the A549 non-small cell lung cancer cells. Oncol Rep. 2014;31(1):298鈥?04.PubMed
  62.Hsu YL, Chia CC, Chen PJ, Huang SE, Huang SC, Kuo PL. Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells. Mol Nutr Food Res. 2009;53(7):826鈥?5.PubMed
  63.鈥?/div>Zheng H, Li Y, Wang Y, Zhao H, Zhang J, Chai H, et al. Downregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance, migration and invasion. Toxicol Appl Pharmacol. 2014;280(1):10鈥?0. PubMed PMID: 25094029. Epub 2014/08/06. Eng. This paper present a unique mechansim for the anticancer activity of iso-liquiritigenin.
  64.Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994;124(4):619鈥?6.PubMed
  65.Simpson CD, Anyiwe K, Schimmer AD. Anoikis resistance and tumor metastasis. Cancer Lett. 2008;272(2):177鈥?5.PubMed
  66.Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9(3):153鈥?6.PubMed
  67.Sherr CJ. D-type cyclins. Trends Biochem Sci. 1995;20(5):187鈥?0.PubMed
  68.Sherr CJ. Cancer cell cycles. Science. 1996;274(5293):1672鈥?.PubMed
  69.Huang W, Tang S, Qiao X, Ma W, Ji S, Wang K, et al. Isoangustone A induces apoptosis in SW480 human colorectal adenocarcinoma cells by disrupting mitochondrial functions. Fitoterapia. 2014;94:36鈥?7.PubMed
  70.Seon MR, Lim SS, Choi HJ, Park SY, Cho HJ, Kim JK, et al. Isoangustone A present in hexane/ethanol extract of Glycyrrhiza uralensis induces apoptosis in DU145 human prostate cancer cells via the activation of DR4 and intrinsic apoptosis pathway. Mol Nutr Food Res. 2010;54(9):1329鈥?9.PubMed
  71.Seon MR, Park SY, Kwon SJ, Lim SS, Choi HJ, Park H, et al. 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(1):85鈥?2.PubMed
  72.鈥⑩€?/div>Lee E, Son JE, Byun S, Lee SJ, Kim YA, Liu K, et al. CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth. Toxicol Appl Pharmacol. 2013;272(1):12鈥?0. PubMed PMID: 23707764. Epub 2013/05/28. eng. One of the first papers to show direct molecular targets of a specific licorice compound.
  73.Vlach J, Hennecke S, Amati B. Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J. 1997;16(17):5334鈥?4.PubMed Central PubMed
  74.Liang J, Zubovitz J, Petrocelli T, Kotchetkov R, Connor MK, Han K, et al. PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med. 2002;8(10):1153鈥?0.PubMed
  75.Tsihlias J, Kapusta LR, DeBoer G, Morava-Protzner I, Zbieranowski I, Bhattacharya N, et al. Loss of cyclin-dependent kinase inhibitor p27Kip1 is a novel prognostic factor in localized human prostate adenocarcinoma. Cancer Res. 1998;58(3):542鈥?.PubMed
  76.Yang RM, Naitoh J, Murphy M, Wang HJ, Phillipson J, de Kernion JB, et al. Low p27 expression predicts poor disease-free survival in patients with prostate cancer. J Urol. 1998;159(3):941鈥?.PubMed
  77.鈥⑩€?/div>Song NR, Lee EJ, Byun S, Kim JE, Mottamal M, Park JH, et al. Isoangustone A, a novel licorice compound, inhibits cell proliferation by targeting PI3-K, MKK4 and MKK7 in human melanoma. Cancer Prev Res (Phila). Oct 8. PubMed PMID: 24104352. Epub 2013/10/10. Eng. One of the first papers to report direct binding partners for a specific licorice compound.
  78.Musgrove EA, Caldon CE, Barraclough J, Stone A, Sutherland RL. Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 2011;11(8):558鈥?2.PubMed
  79.Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135鈥?7.PubMed
  80.Willems L, Tamburini J, Chapuis N, Lacombe C, Mayeux P, Bouscary D. PI3K and mTOR signaling pathways in cancer: new data on targeted therapies. Curr Oncol Rep. 2012;14(2):129鈥?8.PubMed
  81.Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27(41):5497鈥?10.PubMed Central PubMed
  82.Takahashi-Yanaga F, Sasaguri T. GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy. Cell Signal. 2008;20(4):581鈥?.PubMed
  83.Xiao XY, Hao M, Yang XY, Ba Q, Li M, Ni SJ, et al. Licochalcone A inhibits growth of gastric cancer cells by arresting cell cycle progression and inducing apoptosis. Cancer Lett. 2011;302(1):69鈥?5.PubMed
  84.Rafi MM, Rosen RT, Vassil A, Ho CT, Zhang H, Ghai G, et al. Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res. 2000;20(4):2653鈥?.PubMed
  85.Kim YJ, Jung EB, Myung SC, Kim W, Lee CS. Licochalcone A enhances geldanamycin-induced apoptosis through reactive oxygen species-mediated caspase activation. Pharmacology. **;92(1鈥?):49鈥?9. PubMed PMID: 23921841. Epub 2013/08/08. eng.
  86.Lee CS, Kwak SW, Kim YJ, Lee SA, Park ES, Myung SC, et al. Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A on human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathways. Eur J Pharmacol. 2012;683(1鈥?):54鈥?2.PubMed
  87.Kim YH, Shin EK, Kim DH, Lee HH, Park JH, Kim JK. Antiangiogenic effect of licochalcone A. Biochem Pharmacol. 2010;80(8):1152鈥?.PubMed
  88.Park SY, Kim EJ, Choi HJ, Seon MR, Lim SS, Kang YH, et al. Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root. Nutr Res Pract. 2014;8(3):257鈥?6.PubMed Central PubMed
  89.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(18):8266鈥?3.PubMed
  90.Kim JS, Park MR, Lee SY, Kim K, Moon SM, Kim CS, et al. Licochalcone A induces apoptosis in KB human oral cancer cells via a caspase-dependent FasL signaling pathway. Oncol Rep. 2014;31(2):755鈥?2.PubMed Central PubMed
  91.Fu Y, Hsieh TC, Guo J, Kunicki J, Lee MY, Darzynkiewicz Z, et al. Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells. Biochem Biophys Res Commun. 2004;322(1):263鈥?0.PubMed
  92.Park JH, Lim HJ, Lee KS, Lee S, Kwak HJ, Cha JH, et al. Anti-proliferative effect of licochalcone A on vascular smooth muscle cells. Biol Pharm Bull. 2008;31(11):1996鈥?000.PubMed
  93.Kim JK, Shin EK, Park JH, Kim YH. Antitumor and antimetastatic effects of licochalcone A in mouse models. J Mol Med (Berl). 2010;88(8):829鈥?8.
  94.Lee CK, Son SH, Park KK, Park JH, Lim SS, Kim SH, et al. 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(1):48鈥?4.PubMed
  95.Kwon HS, Park JH, Kim DH, Kim YH, Shin HK, Kim JK. Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice. J Mol Med (Berl). 2008;86(11):1287鈥?5.
  96.Furuhashi I, Iwata S, Shibata S, Sato T, Inoue H. Inhibition by licochalcone A, a novel flavonoid isolated from liquorice root, of IL-1beta-induced PGE2 production in human skin fibroblasts. J Pharm Pharmacol. 2005;57(12):1661鈥?.PubMed
  97.Jiang J, Yuan X, Zhao H, Yan X, Sun X, Zheng Q. Licochalcone A inhibiting proliferation of bladder cancer T24 cells by inducing reactive oxygen species production. Biomed Mater Eng. 2014;24(1):1019鈥?5.PubMed
  98.Yuan X, Li D, Zhao H, Jiang J, Wang P, Ma X, et al. Licochalcone A-induced human bladder cancer T24 cells apoptosis triggered by mitochondria dysfunction and endoplasmic reticulum stress. Biomed Res Int. 2013;2013:474272.PubMed Central PubMed
  99.Baldwin Jr AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649鈥?3.PubMed
  100.Schulze-Osthoff K, Ferrari D, Riehemann K, Wesselborg S. Regulation of NF-kappa B activation by MAP kinase cascades. Immunobiology. 1997;198(1鈥?):35鈥?9.PubMed
  101.Gilmore TD. Clinically relevant findings. J Clin Invest. 1997;100(12):2935鈥?.PubMed Central PubMed
  102.Li JJ, Westergaard C, Ghosh P, Colburn NH. Inhibitors of both nuclear factor-kappaB and activator protein-1 activation block the neoplastic transformation response. Cancer Res. 1997;57(16):3569鈥?6.PubMed
  103.Nabel GJ, Verma IM. Proposed NF-kappa B/I kappa B family nomenclature. Genes Dev. 1993;7(11):2063.PubMed
  104.Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006;25(51):6680鈥?.PubMed
  105.Furusawa J, Funakoshi-Tago M, Tago K, Mashino T, Inoue H, Sonoda Y, et al. Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-kappaB p65 phosphorylation at serine 276. Cell Signal. 2009;21(5):778鈥?5.PubMed
  106.Furusawa J, Funakoshi-Tago M, Mashino T, Tago K, Inoue H, Sonoda Y, et al. Glycyrrhiza inflata-derived chalcones, licochalcone A, licochalcone B and licochalcone D, inhibit phosphorylation of NF-kappaB p65 in LPS signaling pathway. Int Immunopharmacol. 2009;9(4):499鈥?07.PubMed
  107.Funakoshi-Tago M, Tanabe S, Tago K, Itoh H, Mashino T, Sonoda Y, et al. Licochalcone A potently inhibits tumor necrosis factor alpha-induced nuclear factor-kappaB activation through the direct inhibition of IkappaB kinase complex activation. Mol Pharmacol. 2009;76(4):745鈥?3.PubMed
  108.Shen H, Zeng G, Tang G, Cai X, Bi L, Huang C, et al. Antimetastatic effects of licochalcone A on oral cancer via regulating metastasis-associated proteases. Tumour Biol. 2014;35(8):7467鈥?4.PubMed
  109.Tsai JP, Hsiao PC, Yang SF, Hsieh SC, Bau DT, Ling CL, et al. Licochalcone A suppresses migration and invasion of human hepatocellular carcinoma cells through downregulation of MKK4/JNK via NF-kappaB mediated urokinase plasminogen activator expression. PLoS ONE. 2014;9(1):e86537.PubMed Central PubMed
  110.Huang HC, Tsai LL, Tsai JP, Hsieh SC, Yang SF, Hsueh JT, et al. Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/-3 expression. Tumour Biol. 2014 Aug 23. PubMed PMID: 25149157. Epub 2014/08/26. Eng.
  111.鈥⑩€?/div>Yao K, Chen H, Lee MH, Li H, Ma W, Peng C, et al. Licochalcone A, a natural inhibitor of c-Jun N-terminal kinase 1. Cancer Prev Res (Phila). 2014;7(1):139鈥?9. PubMed PMID: 24253317. Epub 2013/11/21. Eng. First to report that licochalcone A directly bound to and inhibited JNK1.
  112.Yao K, Cho YY, Bode AM, Vummenthala A, Park JG, Liu K, et al. A selective small-molecule inhibitor of c-Jun N-terminal kinase 1. FEBS Lett. 2009;583(13):2208鈥?2.PubMed
  113.Chang HJ, Yoon G, Park JS, Kim MH, Baek MK, Kim NH, et al. Induction of apoptosis by the licochalcone E in endothelial cells via modulation of NF-kappaB and Bcl-2 Family. Biol Pharm Bull. 2007;30(12):2290鈥?.PubMed
  114.Kwon SJ, Park SY, Kwon GT, Lee KW, Kang YH, Choi MS, et al. Licochalcone E present in licorice suppresses lung metastasis in the 4T1 mammary orthotopic cancer model. Cancer Prev Res (Phila). 2013;6(6):603鈥?3.
  115.Kim SS, Lim J, Bang Y, Gal J, Lee SU, Cho YC, et al. Licochalcone E activates Nrf2/antioxidant response element signaling pathway in both neuronal and microglial cells: therapeutic relevance to neurodegenerative disease. J Nutr Biochem. 2012;23(10):1314鈥?3.PubMed
  116.Lee HN, Cho HJ, Lim Do Y, Kang YH, Lee KW, Park JH. Mechanisms by which licochalcone e exhibits potent anti-inflammatory properties: studies with phorbol ester-treated mouse skin and lipopolysaccharide-stimulated murine macrophages. Int J Mol Sci. 2013;14(6):10926鈥?3.PubMed Central PubMed
  117.Cho YC, Lee SH, Yoon G, Kim HS, Na JY, Choi HJ, et al. Licochalcone E reduces chronic allergic contact dermatitis and inhibits IL-12p40 production through down-regulation of NF-kappa B. Int Immunopharmacol. 2010;10(9):1119鈥?6.PubMed
  
• 作者单位：Ann M. Bode (1)
  Zigang Dong (1)
  
  1. The Hormel Institute University of Minnesota, 801 16th Ave NE, Austin, MN, 55912, USA
  
• 刊物类别：Pharmacology/Toxicology; Biomedicine general; Cancer Research; Molecular Medicine;
• 刊物主题：Pharmacology/Toxicology; Biomedicine general; Cancer Research; Molecular Medicine;
• 出版者：Springer International Publishing
• ISSN：2198-641X

文摘

Cancer is still a major health issue worldwide and identifying novel but safe compounds for prevention and treatment is a high priority. Licorice (Glycyrrhiza) is a perennial plant that is cultivated in many countries and has been reported to exert antioxidant, anti-inflammatory and anticancer effects. However, some components of licorice exert unwanted side effects and therefore identifying safer licorice components would be ideal. The anticancer activities of many of the licorice components appear to include cycle arrest, apoptosis induction, and general antioxidant effects. Commonly reported indirect protein targets important in tumorigenesis include many cell cycle-related proteins, apoptosis-associated proteins, MMP proteins, COX-2, GSK-尾, Akt, NF-魏B, and MAP kinases. Importantly, several licorice components were reported to directly bind to and inhibit the activities of PI3-K, MKK4, MKK7, JNK1, mTOR, and Cdk2, resulting in decreased carcinogenesis in several cell and mouse models with no obvious toxicity. This review focuses on specific components of licorice for which a direct protein target has been identified. Keywords Glycyrrhizic acid Glycyrrhetic acid Iso-liquiritigenin Isoangustone A Licochalcone A Licochalcone E