Planta Med 2015; 81(18): 1670-1687
DOI: 10.1055/s-0035-1558227
Reviews
Georg Thieme Verlag KG Stuttgart · New York

A Systematic Review of the Anticancer Properties of Compounds Isolated from Licorice (Gancao)

Zheng-Hai Tang
1   State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
,
Ting Li
1   State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
,
Yun-Guang Tong
2   Department of Medicine, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, Los Angeles, CA, USA
,
Xiao-Jia Chen
1   State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
,
Xiu-Ping Chen
1   State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
,
Yi-Tao Wang
1   State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
,
Jin-Jian Lu
1   State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
› Author Affiliations
Further Information

Publication History

received 28 April 2015
revised 14 August 2015

accepted 16 October 2015

Publication Date:
22 December 2015 (online)

Abstract

Licorice (Gancao in Chinese) has been used worldwide as a botanical source in medicine and as a sweetening agent in food products for thousands of years. Triterpene saponins and flavonoids are its main ingredients that exhibit a variety of biological activities, including hepatoprotective, antiulcer, anti-inflammatory, antiviral and anticancer effects among others. This review attempts to summarize the current knowledge on the anticancer properties and mechanisms of the compounds isolated from licorice and obtain new insights for further research and development of licorice. A broad spectrum of in vitro and in vivo studies have recently demonstrated that the mixed extracts and purified compounds from licorice exhibit evident anticancer properties by inhibition of proliferation, induction of cell cycle arrest, apoptosis, autophagy, differentiation, suppression of metastasis, angiogenesis, and sensitization of chemotherapy or radiotherapy. A combined treatment of licorice compounds and clinical chemotherapy drugs remarkably enhances anticancer effects and reduces the side effects of chemotherapeutics. Furthermore, glycyrrhizic acid and glycyrrhetinic acid in licorice have been indicated to present obvious liver-targeting effects in targeted drug delivery systems for hepatocellular carcinoma treatment.

 
  • References

  • 1 Blumenthal M, Goldberg A, Brinckmann J editors. Herbal medicine: expanded commission E monographs. Boston, MA: Integrative Medicine Communications; 2000
  • 2 Yang S. The Divine Farmerʼs Materia Medica: A Translation of the Shen Nong Ben Cao Jing. Boulder, CO: Blue Poppy Enterprises, Inc.; 1998
  • 3 Nomura T, Fukai T. Phenolic constituents of licorice (Glycyrrhiza species). In: Herz W, Kirby GW, Moore RE, Steglich W, Tamm C, editors Fortschritte der Chemie organischer Naturstoffe/Progress in the Chemistry of Organic Natural Products, Vol. 73. Vienna: Springer; 1998: 1-140
  • 4 Shibata S. A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice. Yakugaku Zasshi 2000; 120: 849-862
  • 5 Fujita T, Sezik E, Tabata M, Yesilada E, Honda G, Takeda Y, Tanaka T, Takaishi Y. Traditional medicine in Turkey VII. Folk medicine in middle and west Black Sea regions. Econ Bot 1995; 49: 406-422
  • 6 Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res 2008; 22: 709-724
  • 7 Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer 2001; 39: 1-11
  • 8 Nomura T, Fukai T, Akiyama T. Chemistry of phenolic compounds of licorice (Glycyrrhiza species) and their estrogenic and cytotoxic activities. Pure Appl Chem 2002; 74: 1199-1206
  • 9 Zhang Q, Ye M. Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice). J Chromatogr A 2009; 13: 1954-1969
  • 10 Ong ES, Len SM. Pressurized hot water extraction of berberine, baicalein and glycyrrhizin in medicinal plants. Anal Chim Acta 2003; 482: 81-89
  • 11 Li BQ, Wang HB, Li XY, Cheng X. Study on combined extraction of flavonoids and glycyrrhizic acid from Glycyrrhiza by using ultrasonic assisted method. SD J Tradit Chin Med 2005; 24: 38-40
  • 12 Ong ES. Chemical assay of glycyrrhizin in medicinal plants by pressurized liquid extraction (PLE) with capillary zone electrophoresis (CZE). J Sep Sci 2002; 25: 825-831
  • 13 Wang HB, Zhou ZB, Luo F, Yang L. Study on extraction method of flavonoids from Glycyrrhiza and its anti-oxida activity. LSZ Med and Mater Med Res 2008; 19: 2106-2107
  • 14 Cui YM, Yu LJ, Ao MZ, Yang Y, Hu J. Studies on flavonoids extraction technology from Glycyrrhiza inflata and their bacteriostatic activities. J Chin Med Mater 2006; 29: 838-841
  • 15 Commission CP. Pharmacopoeia of the Peopleʼs Republic of China, Part 1 (2010). Beijing: China Medical Science Press; 2010
  • 16 Shin EM, Kim S, Merfort I, Kim YS. Glycyrol induces apoptosis in human Jurkat T cell lymphocytes via the Fas-FasL/caspase-8 pathway. Planta Med 2011; 77: 242-247
  • 17 Shimizu N, Tomoda M, Takada K, Gonda R. The core structure and immunological activities of glycyrrhizan UA, the main polysaccharide from the root of Glycyrrhiza uralensis . Chem Pharm Bull (Tokyo) 1992; 40: 2125-2128
  • 18 Yang G, Yu Y. Immunopotentiating effect of traditional Chinese drugs–ginsenoside and glycyrrhiza polysaccharide. Proc Chin Acad Med Sci Peking Union Med Coll 1990; 5: 188-193
  • 19 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: 1715-1719
  • 20 Popovich DG, Yeo SY, Zhang W. Ginseng (Panax quinquefolius) and licorice (Glycyrrhiza uralensis) root extract combinations increase hepatocarcinoma cell (Hep-G2) viability. Evid Based Complement Alternat Med 2011; 2011: 408273
  • 21 Watanabe M, Hayakawa S, Isemura M, Kumazawa S, Nakayama T, Mori C, Kawakami T. Identification of licocoumarone as an apoptosis-inducing component in licorice. Biol Pharm Bull 2002; 25: 1388-1390
  • 22 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: 1776-1783
  • 23 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: 8266-8273
  • 24 Park SY, Kim EJ, Choi HJ, Seon MR, Lim SS, Kang YH, Choi MS, Lee KW, Park Y, Han J. Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root. Nutr Res Pract 2014; 8: 257-266
  • 25 Chung WT, Lee SH, Kim JD, Sung NS, Hwang B, Lee SY, Yu CY, Lee HY. Effect of the extracts from Glycyrrhiza uralensis Fisch on the growth characteristics of human cell lines: anti-tumor and immune activation activities. Cytotechnology 2001; 37: 55-64
  • 26 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: 239-247
  • 27 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 4 T1 murine mammary cancer cells. J Nutr Biochem 2012; 23: 85-92
  • 28 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: 677-684
  • 29 Seon MR, Lim SS, Choi HJ, Park SY, Cho HJ, Kim JK, Kim J, Kwon DY, Park JH. 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: 1329-1339
  • 30 Sheela ML, Ramakrishna MK, Salimath BP. Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra . Int Immunopharmacol 2006; 6: 494-498
  • 31 Lee CK, Park KK, Lim SS, Park JH, Chung WY. Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. Biol Pharm Bull 2007; 30: 2191-2195
  • 32 Negishi M, Irie A, Nagata N, Ichikawa A. Specific binding of glycyrrhetinic acid to the rat liver membrane. Biochim Biophys Acta 1991; 1066: 77-82
  • 33 Ismair MG, Stanca C, Ha HR, Renner EL, Meier PJ, Kullak-Ublick GA. Interactions of glycyrrhizin with organic anion transporting polypeptides of rat and human liver. Hepatol Res 2003; 26: 343-347
  • 34 Lee CS, Kim YJ, Lee MS, Han ES, Lee SJ. 18β-Glycyrrhetinic acid induces apoptotic cell death in SiHa cells and exhibits a synergistic effect against antibiotic anti-cancer drug toxicity. Life Sci 2008; 83: 481-489
  • 35 Rossi T, Benassi L, Magnoni C, Ruberto AI, Coppi A, Baggio G. Effects of glycyrrhizin on UVB-irradiated melanoma cells. In Vivo 2005; 19: 319-322
  • 36 Lee J, Jung E, Park J, Jung K, Park E, Kim J, Hong S, Park J, Park S, Lee S, Park D. Glycyrrhizin induces melanogenesis by elevating a cAMP level in b16 melanoma cells. J Invest Dermatol 2005; 124: 405-411
  • 37 Chueh FS, Hsiao YT, Chang SJ, Wu PP, Yang JS, Lin JJ, Chung JG, Lai TY. Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase- and mitochondria-dependent pathways. Oncol Rep 2012; 28: 2069-2076
  • 38 He SQ, Gao M, Fu YF, Zhang YN. Glycyrrhizic acid inhibits leukemia cell growth and migration via blocking AKT/mTOR/STAT3 signaling. Int J Clin Exp Pathol 2015; 8: 5175-5181
  • 39 Satomi Y, Nishino H, Shibata S. Glycyrrhetinic acid and related compounds induce G1 arrest and apoptosis in human hepatocellular carcinoma HepG2. Anticancer Res 2005; 25: 4043-4047
  • 40 Huang RY, Chu YL, Jiang ZB, Chen XM, Zhang X, Zeng X. Glycyrrhizin suppresses lung adenocarcinoma cell growth through inhibition of thromboxane synthase. Cell Physiol Biochem 2014; 33: 375-388
  • 41 Li S, Zhu JH, Cao LP, Sun Q, Liu HD, Li JS, Hang CH. Growth inhibitory in vitro effects of glycyrrhizic acid in U251 glioblastoma cell line. Neurol Sci 2014; 35: 1115-1120
  • 42 Thirugnanam S, Xu L, Ramaswamy K, Gnanasekar M. Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. Oncol Rep 2008; 20: 1387-1392
  • 43 Rossi T, Castelli M, Zandomeneghi G, Ruberto A, Benassi L, Magnoni C, Santachiara S, Baggio G. Selectivity of action of glycyrrhizin derivatives on the growth of MCF-7 and HEP-2 cells. Anticancer Res 2003; 23: 3813-3818
  • 44 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: 4053-4058
  • 45 Kobayashi S, Miyamoto T, Kimura I, Kimura M. Inhibitory effect of isoliquiritin, a compound in licorice root, on angiogenesis in vivo and tube formation in vitro . Biol Pharm Bull 1995; 18: 1382-1386
  • 46 Kim KJ, Choi JS, Kim KW, Jeong JW. The anti-angiogenic activities of glycyrrhizic acid in tumor progression. Phytother Res 2013; 27: 841-846
  • 47 Wakamatsu T, Nakahashi Y, Hachimine D, Seki T, Okazaki K. The combination of glycyrrhizin and lamivudine can reverse the cisplatin resistance in hepatocellular carcinoma cells through inhibition of multidrug resistance-associated proteins. Int J Oncol 2007; 31: 1465-1472
  • 48 Sun MF, Chang TT, Chang KW, Huang HJ, Chen HY, Tsai FJ, Lin JG, Chen CY. Blocking the DNA repair system by traditional Chinese medicine?. J Biomol Struct Dyn 2011; 28: 895-906
  • 49 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: 177-186
  • 50 Palumbo R, Sampaolesi M, De Marchis F, Tonlorenzi R, Colombetti S, Mondino A, Cossu G, Bianchi ME. Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation. J Cell Biol 2004; 164: 441-449
  • 51 Shotorbani SS, Su ZL, Xu HX. Toll-like receptors are potential therapeutic targets in rheumatoid arthritis. World J Biol Chem 2011; 2: 167-172
  • 52 Smolarczyk R, Cichon T, Matuszczak S, Mitrus I, Lesiak M, Kobusinska M, Kamysz W, Jarosz M, Sieron A, Szala S. The role of Glycyrrhizin, an inhibitor of HMGB1 protein, in anticancer therapy. Arch Immunol Ther Exp (Warsz) 2012; 60: 391-399
  • 53 Schlueter C, Weber H, Meyer B, Rogalla P, Röser K, Hauke S, Bullerdiek J. Angiogenetic signaling through hypoxia: HMGB1: an angiogenetic switch molecule. Am J Pathol 2005; 166: 1259-1263
  • 54 Mollica L, De Marchis F, Spitaleri A, Dallacosta C, Pennacchini D, Zamai M, Agresti A, Trisciuoglio L, Musco G, Bianchi ME. Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol 2007; 14: 431-441
  • 55 Gong G, Xiang L, Yuan L, Hu L, Wu W, Cai L, Yin L, Dong H. Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on focal cerebral ischemia/reperfusion-induced inflammation, oxidative stress, and apoptosis in rats. PLoS One 2014; 9: e89450
  • 56 Chung JG, Chang HL, Lin WC, Wang HH, Yeh CC, Hung CF, Li YC. Inhibition of N-acetyltransferase activity and DNA-2-aminofluorene adducts by glycyrrhizic acid in human colon tumour cells. Food Chem Toxicol 2000; 38: 163-172
  • 57 Ilett KF, David BM, Detchon P, Castleden WM, Kwa R. Acetylation phenotype in colorectal carcinoma. Cancer Res 1987; 47: 1466-1469
  • 58 Kirlin WG, Trinidad A, Yerokun T, Ogolla F, Ferguson RJ, Andrews AF, Brady PK, Hein DW. Polymorphic expression of acetyl coenzyme A-dependent arylamine N-acetyltransferase and acetyl coenzyme A-dependent O-acetyltransferase-mediated activation of N-hydroxyarylamines by human bladder cytosol. Cancer Res 1989; 49: 2448-2454
  • 59 Umemura T, Tokumo K, Sirma H, Gebhardt R, Poirier MC, Williams GM. Dose response effects of 2-acetylaminofluorene on DNA damage, cytotoxicity, cell proliferation and neoplastic conversion in rat liver. Cancer Lett 1993; 73: 1-10
  • 60 Shi L, Tang C, Yin C. Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma. Biomaterials 2012; 33: 7594-7604
  • 61 Lin A, Chen J, Liu Y, Deng S, Wu Z, Huang Y, Ping Q. Preparation and evaluation of N-caproyl chitosan nanoparticles surface modified with glycyrrhizin for hepatocyte targeting. Drug Dev Ind Pharm 2009; 35: 1348-1355
  • 62 Lin A, Liu Y, Huang Y, Sun J, Wu Z, Zhang X, Ping Q. Glycyrrhizin surface-modified chitosan nanoparticles for hepatocyte-targeted delivery. Int J Pharm 2008; 359: 247-253
  • 63 Niwa K, Lian Z, Onogi K, Yun W, Tang L, Mori H, Tamaya T. Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice. Oncol Rep 2007; 17: 617-622
  • 64 Rahman S, Sultana S. Chemopreventive activity of glycyrrhizin on lead acetate mediated hepatic oxidative stress and its hyperproliferative activity in Wistar rats. Chem Biol Interact 2006; 160: 61-69
  • 65 Rahman S, Sultana S. Glycyrrhizin exhibits potential chemopreventive activity on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in Swiss albino mice. J Enzyme Inhib Med Chem 2007; 22: 363-369
  • 66 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: 187-193
  • 67 Shiota G, Harada K, Ishida M, Tomie Y, Okubo M, Katayama S, Ito H, Kawasaki H. Inhibition of hepatocellular carcinoma by glycyrrhizin in diethylnitrosamine-treated mice. Carcinogenesis 1999; 20: 59-63
  • 68 Csuk R, Schwarz S, Siewert B, Kluge R, Ströhl D. Synthesis and antitumor activity of ring A modified glycyrrhetinic acid derivatives. Eur J Med Chem 2011; 46: 5356-5369
  • 69 Yang JC, Myung SC, Kim W, Lee CS. 18β-Glycyrrhetinic acid potentiates Hsp90 inhibition-induced apoptosis in human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathway. Mol Cell Biochem 2012; 370: 209-219
  • 70 Lee CS, Yang JC, Kim YJ, Jang ER, Kim W, Myung SC. 18Beta-glycyrrhetinic acid potentiates apoptotic effect of trichostatin A on human epithelial ovarian carcinoma cell lines. Eur J Pharmacol 2010; 649: 354-361
  • 71 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: 463-473
  • 72 Luo HL, Zhang ZL, Wu QN, Huang MS, Wei H, Zhang DF, Yang F. 18β-Glycyrrhetinic acid-induced apoptosis and relation with intracellular Ca2+ release in human breast carcinoma cells. Chinese-German J Clin Oncol 2004; 3: 137-140
  • 73 Song J, Ko HS, Sohn EJ, Kim B, Kim JH, Kim HJ, Kim C, Kim JE, Kim SH. 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: 1188-1191
  • 74 Shetty AV, Thirugnanam S, Dakshinamoorthy G, Samykutty A, Zheng G, Chen A, Bosland MC, Kajdacsy-Balla A, Gnanasekar M. 18alpha-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes. Int J Oncol 2011; 39: 635-640
  • 75 Csuk R, Schwarz S, Kluge R, Ströhl D. Synthesis and biological activity of some antitumor active derivatives from glycyrrhetinic acid. Eur J Med Chem 2010; 45: 5718-5723
  • 76 Lin KW, Huang AM, Hour TC, Yang SC, Pu YS, Lin CN. 18β-glycyrrhetinic acid derivatives induced mitochondrial-mediated apoptosis through reactive oxygen species-mediated p 53 activation in NTUB1 cells. Bioorg Med Chem 2011; 19: 4274-4285
  • 77 Liu D, Song D, Guo G, Wang R, Lv J, Jing Y, Zhao L. The synthesis of 18beta-glycyrrhetinic acid derivatives which have increased antiproliferative and apoptotic effects in leukemia cells. Bioorg Med Chem 2007; 15: 5432-5439
  • 78 Yu T, Yamaguchi H, Noshita T, Kidachi Y, Umetsu H, Ryoyama K. Selective cytotoxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells: potential involvement of H-Ras downregulation. Toxicol Lett 2010; 192: 425-430
  • 79 Yamaguchi H, Yu T, Kidachi Y, Akitaya T, Yoshida K, Kamiie K, Noshita T, Umetsu H, Ryoyama K. Selective toxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells is potentially attributed to downregulation of glutathione. Biochimie 2011; 93: 1172-1178
  • 80 Yamaguchi H, Noshita T, Yu T, Kidachi Y, Kamiie K, Umetsu H, Ryoyama K. Novel effects of glycyrrhetinic acid on the central nervous system tumorigenic progenitor cells: induction of actin disruption and tumor cell-selective toxicity. Eur J Med Chem 2010; 45: 2943-2948
  • 81 Sharma G, Kar S, Palit S, Das PK. 18β-Glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells. J Cell Physiol 2012; 227: 1923-1931
  • 82 Zhu J, Chen M, Chen N, Ma A, Zhu C, Zhao R, Jiang M, Zhou J, Ye L, Fu H, Zhang X. Glycyrrhetinic acid induces G1phase cell cycle arrest in human nonsmall cell lung cancer cells through endoplasmic reticulum stress pathway. Int J Oncol 2015; 46: 981-988
  • 83 Tang ZH, Li T, Chang LL, Zhu H, Tong YG, Chen XP, Wang YT, Lu JJ. Glycyrrhetinic acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells. J Agric Food Chem 2014; 62: 11910-11916
  • 84 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: 215-219
  • 85 Jayasooriya RG, Dilshara MG, Park SR, Choi YH, Hyun JW, Chang WY, Kim GY. 18β-Glycyrrhetinic acid suppresses TNF-α induced matrix metalloproteinase-9 and vascular endothelial growth factor by suppressing the Akt-dependent NF-κB pathway. Toxicol In Vitro 2014; 28: 751-758
  • 86 Wang XF, Zhou QM, Lu YY, Zhang H, Huang S, Su SB. Glycyrrhetinic acid potently suppresses breast cancer invasion and metastasis by impairing the p 38 MAPK-AP1 signaling axis. Expert Opin Ther Targets 2015; 19: 577-587
  • 87 Kitagawa S, Nabekura T, Kamiyama S. Inhibition of P-glycoprotein function by tea catechins in KB-C2 cells. J Pharm Pharmacol 2004; 56: 1001-1005
  • 88 Yamaguchi H, Kidachi Y, Kamiie K, Noshita T, Umetsu H, Ryoyama K. Glycyrrhetinic acid induces anoikis-like death and cytoskeletal disruption in the central nervous system tumorigenic cells. Biol Pharm Bull 2010; 33: 321-324
  • 89 Huang R, Li M, Hsin M, Underwood M, Ma L, Mok T, Warner T, Chen G. 4-Methylnitrosamino-1–3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor. Oncogene 2010; 30: 106-116
  • 90 Kuang P, Zhao W, Su W, Zhang Z, Zhang L, Liu J, Ren G, Yin Z, Wang X. 18β-Glycyrrhetinic acid inhibits hepatocellular carcinoma development by reversing hepatic stellate cell-mediated immunosuppression in mice. Int J Cancer 2013; 132: 1831-1841
  • 91 Endo S, Matsunaga T, Soda M, Tajima K, Zhao HT, El-Kabbani O, Hara A. Selective inhibition of the tumor marker AKR1B10 by antiinflammatory N-phenylanthranilic acids and glycyrrhetic acid. Biol Pharm Bull 2010; 33: 886-890
  • 92 Zhang C, Wang W, Liu T, Wu Y, Guo H, Wang P, Tian Q, Wang Y, Yuan Z. Doxorubicin-loaded glycyrrhetinic acid-modified alginate nanoparticles for liver tumor chemotherapy. Biomaterials 2012; 33: 2187-2196
  • 93 Cheng M, Gao X, Wang Y, Chen H, He B, Xu H, Li Y, Han J, Zhang Z. Synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and its inhibition of liver cancer characteristics in vitro and in vivo . Mar Drugs 2013; 11: 3517-3536
  • 94 Tian Q, Wang XH, Wang W, Zhang CN, Wang P, Yuan Z. Self-assembly and liver targeting of sulfated chitosan nanoparticles functionalized with glycyrrhetinic acid. Nanomedicine 2012; 8: 870-879
  • 95 Wang ZY, Agarwal R, Zhou ZC, Bickers DR, Mukhtar H. Inhibition of mutagenicity in Salmonella typhimurium and skin tumor initiating and tumor promoting activities in SENCAR mice by glycyrrhetinic acid: comparison of 18 alpha- and 18 beta-stereoisomers. Carcinogenesis 1991; 12: 187-192
  • 96 Zhang C, Wang W, Liu T, Wu Y, Guo H, Wang P, Tian Q, Wang Y, Yuan Z. Doxorubicin-loaded glycyrrhetinic acid-modified alginate nanoparticles for liver tumor chemotherapy. Biomaterials 2012; 33: 2187-2196
  • 97 Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J. Antiviral effects of Glycyrrhiza species. Phytother Res 2008; 22: 141-148
  • 98 Gupta VK, Fatima A, Faridi U, Negi AS, Shanker K, Kumar J, Rahuja N, Luqman S, Sisodia BS, Saikia D. Antimicrobial potential of Glycyrrhiza glabra roots. J Ethnopharmacol 2008; 116: 377-380
  • 99 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/p 53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells. Mol Nutr Food Res 2009; 53: 826-835
  • 100 Yuan X, Zhang B, Chen N, Chen XY, Liu LL, Zheng QS, Wang ZP. Isoliquiritigenin treatment induces apoptosis by increasing intracellular ROS levels in HeLa cells. J Asian Nat Prod Res 2012; 14: 789-798
  • 101 Hirchaud F, Hermetet F, Ablise M, Fauconnet S, Vuitton DA, Pretet JL, Mougin C. Isoliquiritigenin induces caspase-dependent apoptosis via downregulation of HPV16 E6 expression in cervical cancer Ca ski cells. Planta Med 2013; 79: 1628-1635
  • 102 Zhao H, Yuan X, Li D, Chen H, Jiang J, Wang Z, Sun X, Zheng Q. Isoliquiritigen enhances the antitumour activity and decreases the genotoxic effect of cyclophosphamide. Molecules 2013; 18: 8786-8798
  • 103 Xiao XY, Hao M, Yang XY, Ba Q, Li M, Ni SJ, Wang LS, Du X. Licochalcone A inhibits growth of gastric cancer cells by arresting cell cycle progression and inducing apoptosis. Cancer Lett 2011; 302: 69-75
  • 104 Auyeung KK, Ko JK. Novel herbal flavonoids promote apoptosis but differentially induce cell cycle arrest in human colon cancer cell. Invest New Drugs 2010; 28: 1-13
  • 105 Lee CK, Son SH, Park KK, Park JHY, Lim SS, Chung WY. Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma. J Pharmacol Sci 2008; 106: 444-451
  • 106 Takahashi T, Takasuka N, Iigo M, Baba M, Nishino H, Tsuda H, Okuyama T. Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci 2004; 95: 448-453
  • 107 Kanazawa M, Satomi Y, Mizutani Y, Ukimura O, Kawauchi A, Sakai T, Baba M, Okuyama T, Nishino H, Miki T. Isoliquiritigenin inhibits the growth of prostate cancer. Eur Urol 2003; 43: 580-586
  • 108 Zhang X, Yeung ED, Wang J, Panzhinskiy EE, Tong C, Li W, Li J. Isoliquiritigenin, a natural anti-oxidant, selectively inhibits the proliferation of prostate cancer cells. Clin Exp Pharmacol Physiol 2010; 37: 841-847
  • 109 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: 689-696
  • 110 Chen X, Wu Y, Jiang Y, Zhou Y, Wang Y, Yao Y, Yi C, Gou L, Yang J. Isoliquiritigenin inhibits the growth of multiple myeloma via blocking IL-6 signaling. J Mol Med (Berl) 2012; 90: 1311-1319
  • 111 Li Y, Zhao H, Wang Y, Zheng H, Yu W, Chai H, Zhang J, Falck JR, Guo AM, Yue J, Peng R, Yang J. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3 K/Akt in human breast cancer. Toxicol Appl Pharmacol 2013; 272: 37-48
  • 112 Wang KL, Hsia SM, Chan CJ, Chang FY, Huang CY, Bau DT, Wang PS. Inhibitory effects of isoliquiritigenin on the migration and invasion of human breast cancer cells. Expert Opin Ther Targets 2013; 17: 337-349
  • 113 Li D, Wang Z, Chen H, Wang J, Zheng Q, Shang J, Li J. Isoliquiritigenin induces monocytic differentiation of HL-60 cells. Free Radic Biol Med 2009; 46: 731-736
  • 114 Ii T, Satomi Y, Katoh D, Shimada J, Baba M, Okuyama T, Nishino H, Kitamura N. Induction of cell cycle arrest and p 21(CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin. Cancer Lett 2004; 207: 27-35
  • 115 Hsu YL, Kuo PL, Chiang LC, Lin CC. Isoliquiritigenin inhibits the proliferation and induces the apoptosis of human non-small cell lung cancer a549 cells. Clin Exp Pharmacol Physiol 2004; 31: 414-418
  • 116 Jung SK, Lee MH, Lim do Y, Kim JE, Singh P, Lee SY, Jeong CH, Lim TG, Chen H, Chi YI, Kundu JK, Lee NH, Lee CC, Cho YY, Bode AM, Lee KW, Dong Z. Isoliquiritigenin induces apoptosis and inhibits xenograft tumor growth of human lung cancer cells by targeting both wild type and L858R/T790 M mutant EGFR. J Biol Chem 2014; 289: 35839-35848
  • 117 Yuan X, Yu B, Wang Y, Jiang J, Liu L, Zhao H, Qi W, Zheng Q. Involvement of endoplasmic reticulum stress in isoliquiritigenin-induced SKOV-3 cell apoptosis. Recent Pat Anticancer Drug Discov 2013; 8: 191-199
  • 118 Zhou GS, Song LJ, Yang B. Isoliquiritigenin inhibits proliferation and induces apoptosis of U87 human glioma cells in vitro . Mol Med Rep 2013; 7: 531-536
  • 119 Yamazaki S, Morita T, Endo H, Hamamoto T, Baba M, Joichi Y, Kaneko S, Okada Y, Okuyama T, Nishino H, Tokue A. Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma. Cancer Lett 2002; 183: 23-30
  • 120 Sun C, Zhang H, Ma XF, Zhou X, Gan L, Liu YY, Wang ZH. Isoliquiritigenin enhances radiosensitivity of HepG2 cells via disturbance of redox status. Cell Biochem Biophys 2013; 65: 433-444
  • 121 Hsu YL, Kuo PL, Lin LT, Lin CC. Isoliquiritigenin inhibits cell proliferation and induces apoptosis in human hepatoma cells. Planta Med 2005; 71: 130-134
  • 122 Hsu YL, Kuo PL, Lin CC. Isoliquiritigenin induces apoptosis and cell cycle arrest through p 53-dependent pathway in Hep G2 cells. Life Sci 2005; 77: 279-292
  • 123 Chen X, Zhang B, Yuan X, Yang F, Liu J, Zhao H, Liu L, Wang Y, Wang Z, Zheng Q. Isoliquiritigenin-induced differentiation in mouse melanoma B16F0 cell line. Oxid Med Cell Longev 2012; 12: 1-12
  • 124 Chowdhury SA, Kishino K, Satoh R, Hashimoto K, Kikuchi H, Nishikawa H, Shirataki Y, Sakagami H. Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. Anticancer Res 2005; 25: 2055-2063
  • 125 Kim DC, Ramachandran S, Baek SH, Kwon SH, Kwon KY, Cha SD, Bae I, Cho CH. Induction of growth inhibition and apoptosis in human uterine leiomyoma cells by isoliquiritigenin. Reprod Sci 2008; 15: 552-558
  • 126 Park I, Park KK, Park JHY, Chung WY. Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by inhibiting the metaphase/anaphase transition. Cancer Lett 2009; 277: 174-181
  • 127 Lee CS, Kim YJ, Lee MS, Han ES, Lee SJ. 18Beta-glycyrrhetinic acid induces apoptotic cell death in SiHa cells and exhibits a synergistic effect against antibiotic anti-cancer drug toxicity. Life Sci 2008; 83: 481-489
  • 128 Lee YM, Lim do Y, Choi HJ, Jung JI, Chung WY, Park JH. Induction of cell cycle arrest in prostate cancer cells by the dietary compound isoliquiritigenin. J Med Food 2009; 12: 8-14
  • 129 Takahashi T, Baba M, Nishino H, Okuyama T. Cyclooxygenase-2 plays a suppressive role for induction of apoptosis in isoliquiritigenin-treated mouse colon cancer cells. Cancer Lett 2006; 231: 319-325
  • 130 Yoshida T, Horinaka M, Takara M, Tsuchihashi M, Mukai N, Wakada M, Sakai T. Combination of isoliquiritigenin and tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in colon cancer HT29 cells. Environ Health Prev Med 2008; 13: 281-287
  • 131 Zheng H, Li Y, Wang Y, Zhao H, Zhang J, Chai H, Tang T, Yue J, Guo AM, Yang J. Downregulation of COX-2 and CYP 4 A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis-resistance, migration and invasion. Toxicol Appl Pharmacol 2014; 280: 10-20
  • 132 Chen G, Hu X, Zhang W, Xu N, Wang FQ, Jia J, Zhang WF, Sun ZJ, Zhao YF. Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and apoptotic cell death in adenoid cystic carcinoma cells. Apoptosis 2012; 17: 90-101
  • 133 Ma J, Fu NY, Pang DB, Wu WY, Xu AL. Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells. Planta Med 2001; 67: 754-757
  • 134 Iwashita K, Kobori M, Yamaki K, Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Biosci Biotechnol Biochem 2000; 64: 1813-1820
  • 135 Chen H, Zhang B, Yao Y, Chen N, Chen X, Tian H, Wang Z, Zheng Q. NADPH oxidase-derived reactive oxygen species are involved in the HL-60 cell monocytic differentiation induced by isoliquiritigenin. Molecules 2012; 17: 13424-13438
  • 136 Kwon GT, Cho HJ, Chung WY, Park KK, Moon A, Park JH. Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling. J Nutr Biochem 2009; 20: 663-676
  • 137 Kumar S, Sharma A, Madan B, Singhal V, Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human endothelial cells. Biochem Pharmacol 2007; 73: 1602-1612
  • 138 Kwon HM, Choi YJ, Choi JS, Kang SW, Bae JY, Kang IJ, Jun JG, Lee SS, Lim SS, Kang YH. Blockade of cytokine-induced endothelial cell adhesion molecule expression by licorice isoliquiritigenin through NF-kappaB signal disruption. Exp Biol Med 2007; 232: 235-245
  • 139 Kimura M, Kimura I, Luo B, Kobayashi S. Antiinflammatory effect of Japanese-Sino medicine ʼKeishi-ka-jutsubu-toʼand its component drugs on adjuvant air pouch granuloma of mice. Phytother Res 1991; 5: 195-200
  • 140 Kang SW, Choi JS, Choi YJ, Bae JY, Li J, Kim DS, Kim JL, Shin SY, Lee YJ, Kwun IS, Kang YH. Licorice isoliquiritigenin dampens angiogenic activity via inhibition of MAPK-responsive signaling pathways leading to induction of matrix metalloproteinases. J Nutr Biochem 2010; 21: 55-65
  • 141 Lee KM, Abel J, Ko Y, Harth V, Park WY, Seo JS, Yoo KY, Choi JY, Shin A, Ahn SH. Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women. Br J Cancer 2003; 88: 675-678
  • 142 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: 1028-1036
  • 143 Wong TY, Lin SM, Poon CH, Leung LK. The licorice flavonoid isoliquiritigenin reduces DNA-binding activity of AhR in MCF-7 cells. Chem Biol Interact 2014; 221: 70-76
  • 144 Wang N, Wang Z, Wang Y, Xie X, Shen J, Peng C, You J, Peng F, Tang H, Guan X, Chen J. Dietary compound isoliquiritigenin prevents mammary carcinogenesis by inhibiting breast cancer stem cells through WIF1 demethylation. Oncotarget 2015; 6: 9854-9876
  • 145 Jung JI, Chung E, Seon MR, Shin HK, Kim EJ, Lim SS, Chung WY, Park KK, Park JH. Isoliquiritigenin (ISL) inhibits ErbB3 signaling in prostate cancer cells. Biofactors 2006; 28: 159-168
  • 146 Baba M, Asano R, Takigami I, Takahashi T, Ohmura M, Okada Y, Sugimoto H, Arika T, Nishino H, Okuyama T. Studies on cancer chemoprevention by traditional folk medicines XXV. Inhibitory effect of isoliquiritigenin on azoxymethane-induced murine colon aberrant crypt focus formation and carcinogenesis. Biol Pharm Bull 2002; 25: 247-250
  • 147 Choi AY, Choi JH, Hwang KY, Jeong YJ, Choe W, Yoon KS, Ha J, Kim SS, Youn JH, Yeo EJ, Kang I. Licochalcone A induces apoptosis through endoplasmic reticulum stress via a phospholipase Cgamma1-, Ca-, and reactive oxygen species-dependent pathway in HepG2 human hepatocellular carcinoma cells. Apoptosis 2013; 19: 682-697
  • 148 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
  • 149 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 androgen-independent PC-3 prostate cancer cells. Biochem Biophys Res Commun 2004; 322: 263-270
  • 150 Lee CK, Son SH, Park KK, Park JHY, 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
  • 151 Yoon G, Kang BY, Cheon SH. Topoisomerase I inhibition and cytotoxicity of licochalcones A and E from Glycyrrhiza inflata . Arch Pharm Res 2007; 30: 313-316
  • 152 Lee CS, Kwak SW, Kim YJ, Lee SA, Park ES, Myung SC, Kim W, Lee MS, Lee JJ. 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: 54-62
  • 153 Szliszka E, Jaworska D, Ksek M, Czuba ZP, Król W. Targeting death receptor TRAIL-R2 by chalcones for TRAIL-induced apoptosis in cancer cells. Int J Mol Sci 2012; 13: 15343-15359
  • 154 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: 1019-1025
  • 155 Yuan X, Li D, Zhao H, Jiang J, Wang P, Ma X, Sun X, Zheng Q. Licochalcone A-induced human bladder cancer T24 cells apoptosis triggered by mitochondria dysfunction and endoplasmic reticulum stress. Biomed Res Int 2013; 2013: 474272
  • 156 Cho JJ, Chae JI, Yoon G, Kim KH, Cho JH, Cho SS, Cho YS, Shim JH. Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma. Int J Oncol 2014; 45: 667-674
  • 157 Hao W, Yuan X, Yu L, Gao C, Sun X, Wang D, Zheng Q. Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3 K/AKT signaling pathways. Sci Rep 2015; 5: 1-8
  • 158 Kim JS, Park MR, Lee SY, Kim do K, Moon SM, Kim CS, Cho SS, Yoon G, Im HJ, You JS, Oh JS, Kim SG. Licochalcone A induces apoptosis in KB human oral cancer cells via a caspase-dependent FasL signaling pathway. Oncol Rep 2014; 31: 755-762
  • 159 Park JH, Lim HJ, Lee KS, Lee S, Kwak HJ, Cha JH, Park HY. Anti-proliferative effect of licochalcone A on vascular smooth muscle cells. Biol Pharm Bull 2008; 31: 1996-2000
  • 160 Rafi MM, Rosen RT, Vassil A, Ho CT, Zhang H, Ghai G, Lambert G, DiPaola RS. Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res 1999; 20: 2653-2658
  • 161 Shen H, Zeng G, Tang G, Cai X, Bi L, Huang C, Yang Y. Antimetastatic effects of licochalcone A on oral cancer via regulating metastasis-associated proteases. Tumour Biol 2014; 35: 1-8
  • 162 Kim YH, Shin EK, Kim DH, Lee HH, Park JHY, Kim JK. Antiangiogenic effect of licochalcone A. Biochem Pharmacol 2010; 80: 1152-1159
  • 163 Kim YJ, Jung EB, Myung SC, Kim W, Lee CS. Licochalcone A enhances geldanamycin-induced apoptosis through reactive oxygen species-mediated caspase activation. Pharmacology 2013; 92: 49-59
  • 164 Funakoshi-Tago M, Tago K, Nishizawa C, Takahashi K, Mashino T, Iwata S, Inoue H, Sonoda Y, Kasahara T. Licochalcone A is a potent inhibitor of TEL-Jak2-mediated transformation through the specific inhibition of Stat3 activation. Biochem Pharmacol 2008; 76: 1681-1693
  • 165 Kim JK, Shin EK, Park JH, Kim YH, Park JHY. Antitumor and antimetastatic effects of licochalcone A in mouse models. J Mol Med (Berl) 2010; 88: 829-838
  • 166 Shibata S, Inoue H, Iwata S, Ma RD, Yu LJ, Ueyama H, Takayasu J, Hasegawa T, Tokuda H, Nishino A, Nishino H, Iwashima A. Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice. Planta Med 1991; 57: 221-224
  • 167 Yuan X, Li T, Xiao E, Zhao H, Li Y, Fu S, Gan L, Wang Z, Zheng Q. Licochalcone B inhibits growth of bladder cancer cells by arresting cell cycle progression and inducing apoptosis. Food Chem Toxicol 2014; 65: 242-251
  • 168 Chang HJ, Yoon G, Park JS, Kim MH, Baek MK, Kim NH, Shin BA, Ahn BW, Cheon SH, Jung YD. Induction of apoptosis by the licochalcone E in endothelial cells via modulation of NF-kappaB and Bcl-2 Family. Biol Pharm Bull 2007; 30: 2290-2293
  • 169 Kwon SJ, Park SY, Kwon GT, Lee KW, Kang YH, Choi MS, Yun JW, Jeon JH, Jun JG, Park JH. Licochalcone E present in licorice suppresses lung metastasis in the 4 T1 mammary orthotopic cancer model. Cancer Prev Res 2013; 6: 603-613
  • 170 Zhang SP, Zhou YJ, Liu Y, Cai YQ. Effect of liquiritigenin, a flavanone existed from Radix Glycyrrhizae on pro-apoptotic in SMMC-7721 cells. Food Chem Toxicol 2009; 47: 693-701
  • 171 Liu C, Wang Y, Xie S, Zhou Y, Ren X, Li X, Cai Y. Liquiritigenin induces mitochondria-mediated apoptosis via cytochrome c release and caspases activation in HeLa Cells. Phytother Res 2011; 25: 277-283
  • 172 Wang Y, Xie S, Liu C, Wu Y, Liu Y, Cai Y. Inhibitory effect of liquiritigenin on migration via downregulation proMMP-2 and PI3 K/Akt signaling pathway in human lung adenocarcinoma A549 cells. Nutr Cancer 2012; 64: 627-634
  • 173 Liu Y, Xie S, Wang Y, Luo K, Wang Y, Cai Y. Liquiritigenin inhibits tumor growth and vascularization in a mouse model of HeLa cells. Molecules 2012; 17: 7206-7216
  • 174 Zhou M, Higo H, Cai Y. Inhibition of hepatoma 22 tumor by liquiritigenin. Phytother Res 2010; 24: 827-833
  • 175 Huang W, Tang S, Qiao X, Ma W, Ji S, Wang K, Ye M, Yu S. Isoangustone A induces apoptosis in SW480 human colorectal adenocarcinoma cells by disrupting mitochondrial functions. Fitoterapia 2014; 30: 36-47
  • 176 Lee E, Son JE, Byun S, Lee SJ, Kim YA, Liu K, Kim J, Lim SS, Park JH, Dong Z, Lee KW, Lee HJ. CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth. Toxicol Appl Pharmacol 2013; 272: 12-20
  • 177 Song NR, Lee E, Byun S, Kim JE, Mottamal M, Park JH, Lim SS, Bode AM, Lee HJ, Lee KW, Dong Z. Isoangustone A, a novel licorice compound, inhibits cell proliferation by targeting PI3 K, MKK4, and MKK7 in human melanoma. Cancer Prev Res 2013; 6: 1293-1303
  • 178 Tsai YM, Yang CJ, Hsu YL, Wu LY, Tsai YC, Hung JY, Lien CT, Huang MS, Kuo PL. Glabridin inhibits migration, invasion, and angiogenesis of human non-small cell lung cancer A549 cells by inhibiting the FAK/rho signaling pathway. Integr Cancer Ther 2011; 10: 341-349
  • 179 Hsu YL, Wu LY, Hou MF, Tsai EM, Lee JN, Liang HL, Jong YJ, Hung CH, Kuo PL. Glabridin, an isoflavan from licorice root, inhibits migration, invasion and angiogenesis of MDA-MB-231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway. Mol Nutr Food Res 2011; 55: 318-327
  • 180 Hsieh MJ, Lin CW, Yang SF, Chen MK, Chiou HL. Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF-kappaB and AP-1 activity in human liver cancer cells. Br J Pharmacol 2014; 171: 3037-3050
  • 181 Veratti E, Rossi T, Giudice S, Benassi L, Bertazzoni G, Morini D, Azzoni P, Bruni E, Giannetti A, Magnoni C. 18Beta-glycyrrhetinic acid and glabridin prevent oxidative DNA fragmentation in UVB-irradiated human keratinocyte cultures. Anticancer Res 2011; 31: 2209-2215
  • 182 Park SY, Lim SS, Kim JK, Kang IJ, Kim JS, Lee C, Kim J, Park JH. Hexane-ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells. Br J Nutr 2010; 104: 1272-1282
  • 183 Zhou B, Zhang J, Wu S, Zhuo Q, Gao W, Hao J, Man S. The influence of compatibility of processed Radix Aconiti Kusnezoffii on the pharmacokinetic of four components in Glycyrrhiza uralensis Fisch. J Ethnopharmacol 2015; 169: 1-7
  • 184 Lee YK, Chin YW, Bae JK, Seo JS, Choi YH. Pharmacokinetics of isoliquiritigenin and its metabolites in rats: low bioavailability is primarily due to the hepatic and intestinal metabolism. Planta Med 2013; 79: 1656-1665
  • 185 Kang HE, Jung HY, Cho YK, Kim SH, Sohn SI, Baek SR, Lee MG. Pharmacokinetics of liquiritigenin in mice, rats, rabbits, and dogs, and animal scale-up. J Pharm Sci 2009; 98: 4327-4342
  • 186 Wu YP, Meng XS, Bao YR, Wang S. Pharmacokinetic study of four flavones of Glycyrrhiza in rat plasma using HPLC-MS. J Ethnopharmacol 2013; 148: 266-270
  • 187 Dudgeon DD, Shinde S, Hua Y, Shun TY, Lazo JS, Strock CJ, Giuliano KA, Taylor DL, Johnston PA, Johnston PA. Implementation of a 220,000-compound HCS campaign to identify disruptors of the interaction between p 53 and hDM2 and characterization of the confirmed hits. J Biomol Screen 2010; 15: 766-782
  • 188 Youns M, Efferth T, Reichling J, Fellenberg K, Bauer A, Hoheisel JD. Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells. Biochem Pharmacol 2009; 78: 273-283
  • 189 Wang X, Wei Y, Yuan S, Liu G, Lu Y, Zhang J, Wang W. Potential anticancer activity of tanshinone IIA against human breast cancer. Int J Cancer 2005; 116: 799-807
  • 190 Toledo-Sherman L, Deretey E, Slon-Usakiewicz JJ, Ng W, Dai JR, Foster JE, Redden PR, Uger MD, Liao LC, Pasternak A, Reid N. Frontal affinity chromatography with MS detection of EphB2 tyrosine kinase receptor. 2. Identification of small-molecule inhibitors via coupling with virtual screening. J Med Chem 2005; 48: 3221-3230
  • 191 Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol 2013; 150: 781-790
  • 192 Lauren DR, Jensen DJ, Douglas JA, Follett JM. Efficient method for determining the glycyrrhizin content of fresh and dried roots, and root extracts, of Glycyrrhiza species. Phytochem Anal 2001; 12: 332-335
  • 193 Pang X, Zhang L, Wu Y, Lin L, Li J, Qu W, Safe S, Liu M. Methyl 2-cyano-3, 11-dioxo-18-olean-1, 12-dien-30-oate (CDODA-Me), a derivative of glycyrrhetinic acid, functions as a potent angiogenesis inhibitor. J Pharmacol Exp Ther 2010; 335: 172-179
  • 194 Logashenko EB, Salomatina OV, Markov A, Korchagina DV, Salakhutdinov NF, Tolstikov GA, Vlassov VV, Zenkova MA. Synthesis and pro-apoptotic activity of novel glycyrrhetinic acid derivatives. Chembiochem 2011; 12: 784-794
  • 195 Salomatina OV, Markov AV, Logashenko EB, Korchagina DV, Zenkova MA, Salakhutdinov NF, Vlassov VV, Tolstikov GA. Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and NO production in LPS-activated J-774 cells. Bioorg Med Chem 2014; 22: 585-593