Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma

Phytotherapy Research

Volumn 30, Issue 6, 2016, Pages 863-877

  Chen, Shao Ru ^a   Qiu, Hong Cong ^b   Hu, Yang ^a   Wang, Ying ^a   Wang, Yi Tao ^a  

^a University of Macau   (Macao)

^b Guangxi Institute of Traditional Medical & Pharmaceutical Sciences   (China)

Author keywords

Chinese medicine; Hepatocellular carcinoma; Herbal medicine

Indexed keywords

BAICALEIN; BETA CATENIN; CELL RECEPTOR; CORILAGIN; FUZHENG HUAYU; GLABRIDIN; HERBACEOUS AGENT; HIPPO PROTEIN; HUANGLIAN JIEDU; JIEDUFANG; KANGLAITE; NATURAL PRODUCT; NIVOLUMAB; NOBILETIN; NOTCH RECEPTOR; PHY 906; PHYTOL; PLANT MEDICINAL PRODUCT; REGULATOR PROTEIN; RESVERATROL; SHENQI MIXTURE; SHI QUAN DA BU TANG; SILIBININ; SILIBININ PHOSPHATIDYLCHOLINE COMPLEX; SONIC HEDGEHOG PROTEIN; SORAFENIB; UNCLASSIFIED DRUG; WNT PROTEIN; YES ASSOCIATED PROTEIN;

ANTINEOPLASTIC ACTIVITY; CANCER CHEMOTHERAPY; CANCER STEM CELL; CANCER THERAPY; CELL MATURATION; CELL NUCLEUS; CELLULAR DISTRIBUTION; CLINICAL TRIAL (TOPIC); CYTOSOL; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG TARGETING; GLYCYRRHIZA GLABRA; HERBAL MEDICINE; HUMAN; INTRACELLULAR SIGNALING; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; MOLECULARLY TARGETED THERAPY; NONHUMAN; REVIEW; WNT SIGNALING PATHWAY; CARCINOMA, HEPATOCELLULAR; LIVER NEOPLASMS; PATHOLOGY; PROCEDURES;

CARCINOMA, HEPATOCELLULAR; HERBAL MEDICINE; HUMANS; LIVER NEOPLASMS;

EID: 84959131973     PISSN: 0951418X     EISSN: 10991573     Source Type: Journal    
DOI: 10.1002/ptr.5594     Document Type: Review

References (152)

1. Adianti M, Aoki C, Komoto M, et al.; 2014. Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species. Microbiol Immunol 58 (3): 180-187.
2. Akiyama T, Dass CR, Choong PF,. 2009. Bim-targeted cancer therapy: a link between drug action and underlying molecular changes. Mol Cancer Ther 8 (12): 3173-3180.
3. Amakye D, Jagani Z, Dorsch M,. 2013. Unraveling the therapeutic potential of the Hedgehog pathway in cancer. Nat Med 19 (11): 1410-1422.
4. Arzumanyan A, Reis HM, Feitelson MA,. 2013. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer 13 (2): 123-135.
5. Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN,. 2010. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 51 (6): 1972-1978.
6. Basar N, Oridupa OA, Ritchie KJ, et al.; 2015. Comparative cytotoxicity of Glycyrrhiza glabra roots from different geographical origins against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cells. Phytother Res 29 (6): 944-948.
7. Bassilana F, Carlson A, DaSilva JA, et al.; 2014. Target identification for a Hedgehog pathway inhibitor reveals the receptor GPR39. Nat Chem Biol 10 (5): 343-349.
8. Bertino G, Demma S, Ardiri A, et al.; 2015. The immune system in hepatocellular carcinoma and potential new immunotherapeutic strategies. Biomed Res Int 2015 731469:.
9. Bishayee A, Barnes KF, Bhatia D, Darvesh AS, Carroll RT,. 2010. Resveratrol suppresses oxidative stress and inflammatory response in diethylnitrosamine-initiated rat hepatocarcinogenesis. Cancer Prev Res (Phila) 3 (6): 753-763.
10. Bosch-Barrera J, Menendez JA,. 2015. Silibinin and STAT3: a natural way of targeting transcription factors for cancer therapy. Cancer Treat Rev 41 (6): 540-546.
11. Brandon-Warner E, Sugg JA, Schrum LW, McKillop IH,. 2010. Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma. Cancer Lett 291 (1): 120-129.
12. Breous E, Thimme R,. 2011. Potential of immunotherapy for hepatocellular carcinoma. J Hepatol 54 (4): 830-834.
13. Cai H, Scott E, Kholghi A, et al.; 2015. Cancer chemoprevention: evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice. Sci Transl Med 7 (298 298ra117):.
14. Chan IS, Guy CD, Chen Y, et al.; 2012. Paracrine Hedgehog signaling drives metabolic changes in hepatocellular carcinoma. Cancer Res 72 (24): 6344-6350.
15. Chen B, Dodge ME, Tang W, et al.; 2009. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol 5 (2): 100-107.
16. Chen Z, Chen HY, Lang QB, et al.; 2012. Preventive effects of jiedu granules combined with cinobufacini injection versus transcatheter arterial chemoembolization in post-surgical patients with hepatocellular carcinoma: a case-control trial. Chin J Integr Med 18 (5): 339-344.
17. Chen QL, Lu YY, Peng JH, et al.; 2015. Dynamical regulation analysis identifies molecular mechanisms of Fuzheng-Huayu formula against hepatitis B-caused liver cirrhosis. Evid Based Complement Alternat Med 2015 238495:.
18. Chiba T, Iwama A, Yokosuka O,. 2015. Cancer stem cells in hepatocellular carcinoma: therapeutic implications based on stem cell biology. Hepatol Res 46: 50-57.
19. Cichocki M, Baer-Dubowska W, Wierzchowski M, Murias M, Jodynis-Liebert J,. 2014. 3,4,5,4′-Trans-tetramethoxystilbene (DMU-212) modulates the activation of NF-kappaB, AP-1, and STAT3 transcription factors in rat liver carcinogenesis induced by initiation-promotion regimen. Mol Cell Biochem 391 (1-2): 27-35.
20. Clevers H,. 2006. Wnt/beta-catenin signaling in development and disease. Cell 127 (3): 469-480.
21. Collins FS, Varmus H,. 2015. A new initiative on precision medicine. N Engl J Med 372 (9): 793-795.
22. Croquelois A, Blindenbacher A, Terracciano L, et al.; 2005. Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice. Hepatology 41 (3): 487-496.
23. Dai W, Wang F, Lu J, et al.; 2015. By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice. Oncotarget 6 (15): 13703-13717.
24. Dorchak J, Iida J, Clancy R, et al.; 2012. Abstract P1-05-09: FH535 inhibited migration and growth of breast cancer cells. Cancer Res 72 (24 Supplement): P1-05-09-P01-05-09.
25. Eguchi M, Nguyen C, Lee SC, Kahn M,. 2005. ICG-001, a novel small molecule regulator of TCF/beta-catenin transcription. Med Chem 1 (5): 467-472.
26. Ertle J, Dechene A, Sowa JP, et al.; 2011. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 128 (10): 2436-2443.
27. van Es JH, van Gijn ME, Riccio O, et al.; 2005. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435 (7044): 959-963.
28. Fan XX, Yao XJ, Xu SW, et al.; 2015. (Z)3,4,5,4′-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level. Sci Rep 5: 16348.
29. Fu F, Wan Y, Mulati, Wu T,. 2014. Kanglaite injection combined with hepatic arterial intervention for unresectable hepatocellular carcinoma: a meta-analysis. J Cancer Res Ther 10 (Suppl 1): 38-41.
30. Gambari R, Hau DK, Wong WY, Chui CH,. 2014. Sensitization of Hep3B hepatoma cells to cisplatin and doxorubicin by corilagin. Phytother Res 28 (5): 781-783.
31. Gandhirajan RK, Staib PA, Minke K, et al.; 2010. Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Neoplasia 12 (4): 326-335.
32. Gao Q, Yuan Y, Gan HZ, Peng Q,. 2015. Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis. Oncol Lett 9 (5): 2381-2387.
33. Garg R, Benedetti LG, Abera MB, Wang H, Abba M, Kazanietz MG,. 2014. Protein kinase C and cancer: what we know and what we do not. Oncogene 33 (45): 5225-5237.
34. Gonnissen A, Isebaert S, Haustermans K,. 2015. Targeting the Hedgehog signaling pathway in cancer: beyond Smoothened. Oncotarget 6 (16): 13899-13913.
35. Gordon MS, Robert F, Matei D, et al.; 2014. An open-label phase Ib dose-escalation study of TRC105 (anti-endoglin antibody) with bevacizumab in patients with advanced cancer. Clin Cancer Res 20 (23): 5918-5926.
36. Gramantieri L, Ferracin M, Fornari F, et al.; 2007a. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 67 (13): 6092-6099.
37. Gramantieri L, Giovannini C, Lanzi A, et al.; 2007b. Aberrant Notch3 and Notch4 expression in human hepatocellular carcinoma. Liver Int 27 (7): 997-1007.
38. Greten TF, Manns MP, Korangy F,. 2006. Immunotherapy of hepatocellular carcinoma. J Hepatol 45 (6): 868-878.
39. Gwak J, Lee JH, Chung YH, Song GY, Oh S,. 2012. Small molecule-based promotion of PKCalpha-mediated beta-catenin degradation suppresses the proliferation of CRT-positive cancer cells. PLoS One 7 (10 e46697):.
40. Han SX, Bai E, Jin GH, et al.; 2014. Expression and clinical significance of YAP, TAZ, and AREG in hepatocellular carcinoma. J Immunol Res 2014: 261365.
41. Handeli S, Simon JA,. 2008. A small-molecule inhibitor of Tcf/beta-catenin signaling down-regulates PPARgamma and PPARdelta activities. Mol Cancer Ther 7 (3): 521-529.
42. Hao Y, Xu B-w, Wang Y-g, Wang Q, Qiu Q-y, Huang Q-f,. 2007. Effect of Yiqi Huoxue Jiedu Fang on the growth, metastasis and angiogenesis of Lewis lung carcinomas [J]. Chin J Pathophysiol 1: 030.
43. Hao M, Zheng S, Ding H, Huang A,. 2011. Regulation of microRNA-122 on HBV replication by targeting HBx sequence. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 28 (4): 784-789 803.
44. Harvey KF, Zhang X, Thomas DM,. 2013. The Hippo pathway and human cancer. Nat Rev Cancer 13 (4): 246-257.
45. Hashimoto E, Tokushige K,. 2012. Hepatocellular carcinoma in non-alcoholic steatohepatitis: growing evidence of an epidemic? Hepatol Res 42 (1): 1-14.
46. Hau DK, Zhu GY, Leung AK, et al.; 2010. In vivo anti-tumour activity of corilagin on Hep3B hepatocellular carcinoma. Phytomedicine 18 (1): 11-15.
47. Hayashi I, Takatori S, Urano Y, et al.; 2012. Neutralization of the gamma-secretase activity by monoclonal antibody against extracellular domain of nicastrin. Oncogene 31 (6): 787-798.
48. He N, Zhang Z,. 2015. Baicalein suppresses the viability of MG-63 osteosarcoma cells through inhibiting c-MYC expression via Wnt signaling pathway. Mol Cell Biochem 405 (1-2): 187-196.
49. Henderson WR Jr, Chi EY, Ye X, et al.; 2010. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A 107 (32): 14309-14314.
50. Ho SY, Keller TH,. 2015. The use of porcupine inhibitors to target Wnt-driven cancers. Bioorg Med Chem Lett 25 (23): 5472-5476.
51. Hou Y-x, Yang Z-y, Wang X-b,. 2012. Effect of the induced differentiation and the mechanism of Liangxue Jiedu Fang on hepatic oval cells. China J Tradit Chin Med Pharm 8: 022.
52. Howells LM, Berry DP, Elliott PJ, et al.; 2011. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases-safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res (Phila) 4 (9): 1419-1425.
53. Hsieh MJ, Lin CW, Yang SF, Chen MK, Chiou HL,. 2014. 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 171 (12): 3037-3050.
54. Hsu YL, Kuo PL, Tzeng TF, et al.; 2008. Huang-lian-jie-du-tang, a traditional Chinese medicine prescription, induces cell-cycle arrest and apoptosis in human liver cancer cells in vitro and in vivo. J Gastroenterol Hepatol 23 (7 Pt 2): e290-299.
55. Hu J, Dong A, Fernandez-Ruiz V, et al.; 2009. Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res 69 (17): 6951-6959.
56. Hu Y, Wang S, Wu X, et al.; 2013. Chinese herbal medicine-derived compounds for cancer therapy: a focus on hepatocellular carcinoma. J Ethnopharmacol 149 (3): 601-612.
57. Huang SM, Chien LY, Tai CJ, Chiou JF, Chen CS, Tai CJ,. 2013. Effectiveness of 3-week intervention of Shi Quan Da Bu Tang for alleviating hematotoxicity among patients with breast carcinoma receiving chemotherapy. Integr Cancer Ther 12 (2): 136-144.
58. Huang X, Qin J, Lu S,. 2014. Kanglaite stimulates anticancer immune responses and inhibits HepG2 cell transplantationinduced tumor growth. Mol Med Rep 10 (4): 2153-2159.
59. Iida J, Dorchak J, Lehman JR, et al.; 2012. FH535 inhibited migration and growth of breast cancer cells. PLoS One 7 (9): e44418.
60. Inaguma S, Riku M, Ito H, Tsunoda T, Ikeda H, Kasai K,. 2015. GLI1 orchestrates CXCR4/CXCR7 signaling to enhance migration and metastasis of breast cancer cells. Oncotarget 6 (32): 33648-33657.
61. Infante P, Alfonsi R, Botta B, Mori M, Di Marcotullio L,. 2015. Targeting GLI factors to inhibit the Hedgehog pathway. Trends Pharmacol Sci 36 (8): 547-558.
62. Jaffe S,. 2015. Planning for US Precision Medicine Initiative underway. Lancet 385 (9986): 2448-2449.
63. Jangra RK, Yi M, Lemon SM,. 2010. Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol 84 (13): 6615-6625.
64. Ji Q, Liu X, Fu X, et al.; 2013. Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/beta-catenin signal pathway. PLoS One 8 (11): e78700.
65. Jia L, Jin H, Zhou J, et al.; 2013. A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-beta signaling pathways. BMC Complement Altern Med 13: 33.
66. Jia L, Jin H, Lv M, et al.; 2015. Corilagin, an anti-tumor herb medicine, sensitizes paclitaxel and carboplatin by primarily inhibiting glycolysis pathways in epithelial ovarian cancer. Cancer Res 75 (15 Supplement): 5550-5550.
67. Jiang K, Wang W, Jin X, Wang Z, Ji Z, Meng G,. 2015. Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells. Oncol Rep 33 (6): 2711-2718.
68. Johnson R, Halder G,. 2014. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov 13 (1): 63-79.
69. Kahn M,. 2014. Can we safely target the WNT pathway? Nat Rev Drug Discov 13 (7): 513-532.
70. Katoh M,. 2005. WNT/PCP signaling pathway and human cancer (review). Oncol Rep 14 (6): 1583-1588.
71. Kidd P, Head K,. 2005. A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos). Altern Med Rev 10 (3): 193-203.
72. Kim CW, Lee HJ, Jung JH, et al.; 2015. Activation of caspase-9/3 and inhibition of epithelial mesenchymal transition are critically involved in antitumor effect of phytol in hepatocellular carcinoma cells. Phytother Res 29 (7): 1026-1031.
73. Kiratipaiboon C, Tengamnuay P, Chanvorachote P,. 2015. Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells. Phytomedicine 22 (14): 1269-1278.
74. Lam W, Bussom S, Guan F, et al.; 2010. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Transl Med 2 (45): 45ra59.
75. Lam W, Jiang Z, Guan F, et al.; 2015. PHY906(KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment. Sci Rep 5: 9384.
76. Lim CB, Prele CM, Baltic S, et al.; 2015. Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis. Oncotarget 6 (3): 1519-1530.
77. Lin JJ, Jin CN, Zheng ML, Ouyang XN, Zeng JX, Dai XH,. 2005. Clinical study on treatment of primary hepatocellular carcinoma by Shenqi mixture combined with microwave coagulation. Chin J Integr Med 11 (2): 104-110.
78. Liu SH, Cheng YC,. 2012. Old formula, new Rx: the journey of PHY906 as cancer adjuvant therapy. J Ethnopharmacol 140 (3): 614-623.
79. Liu W-x, Wang J-p, Lin L-h, Zheng H-n, Sun Y,. 2013. Analgesic, anti-inflammatory and in vivo antitumor effects of Huanglianjiedu decoction [J]. J Shenyang Medical College 15 (1): 53-55.
80. Liu YZ, Wu K, Huang J, et al.; 2014. The PTEN/PI3K/Akt and Wnt/beta-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation. Int J Oncol 45 (1): 104-112.
81. Llovet JM, Di Bisceglie AM, Bruix J, et al.; 2008a. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100 (10): 698-711.
82. Llovet JM, Ricci S, Mazzaferro V, et al.; 2008b. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359 (4): 378-390.
83. Ma X, Jin S, Zhang Y, Wan L, Zhao Y, Zhou L,. 2014. Inhibitory effects of nobiletin on hepatocellular carcinoma in vitro and in vivo. Phytother Res 28 (4): 560-567.
84. Mazumdar T, Devecchio J, Agyeman A, Shi T, Houghton JA,. 2011. Blocking Hedgehog survival signaling at the level of the GLI genes induces DNA damage and extensive cell death in human colon carcinoma cells. Cancer Res 71 (17): 5904-5914.
85. Mbimba T, Awale P, Bhatia D, et al.; 2012. Alteration of hepatic proinflammatory cytokines is involved in the resveratrol-mediated chemoprevention of chemically-induced hepatocarcinogenesis. Curr Pharm Biotechnol 13 (1): 229-234.
86. McDermott DF, Atkins MB,. 2013. PD-1 as a potential target in cancer therapy. Cancer Med 2 (5): 662-673.
87. Ming L, Thorgeirsson SS, Gail MH, et al.; 2002. Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China. Hepatology 36 (5): 1214-1220.
88. Mo W, Xu X, Xu L, et al.; 2011. Resveratrol inhibits proliferation and induces apoptosis through the hedgehog signaling pathway in pancreatic cancer cell. Pancreatology 11 (6): 601-609.
89. Nabavi SF, Li H, Daglia M, Nabavi SM,. 2014. Resveratrol and stroke: from chemistry to medicine. Curr Neurovasc Res 11 (4): 390-397.
90. Nagaraj SRM, Lingaraj SM, Balaraju Y, Kumar A, Salimath BP,. 2012. MTA1 induced angiogenesis, migration and tumor growth is inhibited by Glycyrrhiza glabra. IOSR J Pharm 2 (4): 34-43.
91. Nambiar DK, Rajamani P, Deep G, Jain AK, Agarwal R, Singh RP,. 2015. Silibinin preferentially radiosensitizes prostate cancer by inhibiting DNA repair signaling. Mol Cancer Ther 14 (12): 2722-2734.
92. Nambotin SB, Lefrancois L, Sainsily X, et al.; 2011. Pharmacological inhibition of Frizzled-7 displays anti-tumor properties in hepatocellular carcinoma. J Hepatol 54 (2): 288-299.
93. Nault JC,. 2014. Pathogenesis of hepatocellular carcinoma according to aetiology. Best Pract Res Clin Gastroenterol 28 (5): 937-947.
94. Nedelcu D, Liu J, Xu Y, Jao C, Salic A,. 2013. Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling. Nat Chem Biol 9 (9): 557-564.
95. Nencini A, Pratelli C, Quinn JM, et al.; 2015. Structure-activity relationship and properties optimization of a series of quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway. Eur J Med Chem 95: 526-545.
96. Ng JM, Curran T,. 2011. The Hedgehog's tale: developing strategies for targeting cancer. Nat Rev Cancer 11 (7): 493-501.
97. Niu F-W, Zhang Y-J, Li K, Zhang M-S,. 2014. Nobiletin acts as a potential anticancer agent against osteosarcoma by regulating ERK and AKT signaling pathways. Bangladesh J Pharmacol 9 (3): 406-412.
98. Petrova E, Rios-Esteves J, Ouerfelli O, Glickman JF, Resh MD,. 2013. Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling. Nat Chem Biol 9 (4): 247-249.
99. Pez F, Lopez A, Kim M, Wands JR, Caron de Fromentel C, Merle P,. 2013. Wnt signaling and hepatocarcinogenesis: molecular targets for the development of innovative anticancer drugs. J Hepatol 59 (5): 1107-1117.
100. Poduri CD,. 2003. Hepatitis C virus (HCV)-a review molecular biology of the virus, immunodiagnostics, genomic heterogeneity and the role of virus in hepatocellular carcinoma. Indian J Exp Biol 41 (6): 549-562.
101. Qin Y, Ma Z, Dang X, Li W, Ma Q,. 2014. Effect of resveratrol on proliferation and apoptosis of human pancreatic cancer MIA PaCa-2 cells may involve inhibition of the Hedgehog signaling pathway. Mol Med Rep 10 (5): 2563-2567.
102. Ranganathan P, Weaver KL, Capobianco AJ,. 2011. Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer 11 (5): 338-351.
103. Rasool M, Rashid S, Arooj M, et al.; 2014. New possibilities in hepatocellular carcinoma treatment. Anticancer Res 34 (4): 1563-1571.
104. Rockwell S, Grove TA, Liu Y, Cheng YC, Higgins SA, Booth CJ,. 2013. Preclinical studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as a potential adjunct to radiation therapy. Int J Radiat Biol 89 (1): 16-25.
105. Rubin LL, de Sauvage FJ,. 2006. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov 5 (12): 1026-1033.
106. Rui X, Yan X, Zhang K,. 2016. Baicalein inhibits the migration and invasion of colorectal cancer cells via suppression of the AKT signaling pathway. Oncol Lett 11 (1): 685-688.
107. Saif MW, Li J, Lamb L, et al.; 2014. First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer. Cancer Chemother Pharmacol 73 (2): 373-380.
108. Sanyal A, Poklepovic A, Moyneur E, Barghout V,. 2010. Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin 26 (9): 2183-2191.
109. Schmidt OT, Lademann R,. 1951. Corilagin, ein weiterer kristallisierter Gerbstoff aus Dividivi. X. Mitteilung über natürliche Gerbstoffe. Justus Liebigs Ann Chem 571 (3): 232-237.
110. Sicklick JK, Li YX, Jayaraman A, et al.; 2006. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis 27 (4): 748-757.
111. Siegel AB, Narayan R, Rodriguez R, et al.; 2014. A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma. Integr Cancer Ther 13 (1): 46-53.
112. Singh CK, Ndiaye MA, Ahmad N,. 2015. Resveratrol and cancer: challenges for clinical translation. Biochim Biophys Acta 1852 (6): 1178-1185.
113. Song YN, Sun JJ, Lu YY, et al.; 2013. Therapeutic efficacy of fuzheng-huayu tablet based traditional chinese medicine syndrome differentiation on hepatitis-B-caused cirrhosis: a multicenter double-blind randomized controlled trail. Evid Based Complement Alternat Med 2013: 709305.
114. Srivastava RK, Rodova M, Fu J, Nall D, Shankar S,. 2012. Abstract A45: resveratrol inhibits prostate cancer stem cell characteristics by suppressing Wnt, sonic hedgehog, and Notch pathways. Cancer Res 72 (4 Supplement): A45-A45.
115. Stanton BZ, Peng LF, Maloof N, et al.; 2009. A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol 5 (3): 154-156.
116. Su YC, Li SC, Wu YC, Wang LM, Chao KS, Liao HF,. 2013. Resveratrol downregulates interleukin-6-stimulated sonic hedgehog signaling in human acute myeloid leukemia. Evid Based Complement Alternat Med 2013: 547430.
117. Suarez MI, Uribe D, Jaramillo CM, et al.; 2015. Wnt/beta-catenin signaling pathway in hepatocellular carcinomas cases from Colombia. Ann Hepatol 14 (1): 64-74.
118. Sun Z, Lu P, Gail MH, et al.; 1999. Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology 30 (2): 379-383.
119. Takase H, Imanishi K, Miura O, Yumioka E, Watanabe H,. 1989. Features of the anti-ulcer effects of Oren-gedoku-to (a traditional Chinese medicine) and its component herb drugs. Jpn J Pharmacol 49 (3): 301-308.
120. Tang YQ, Jaganath IB, Sekaran SD,. 2010. Phyllanthus spp. induces selective growth inhibition of PC-3 and MeWo human cancer cells through modulation of cell cycle and induction of apoptosis. PLoS One 5 (9): e12644.
121. Tang ZH, Li T, Chang LL, et al.; 2014. Glycyrrhetinic acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells. J Agric Food Chem 62 (49): 11910-11916.
122. Thein HH, Walter SR, Gidding HF, et al.; 2011. Trends in incidence of hepatocellular carcinoma after diagnosis of hepatitis B or C infection: a population-based cohort study, 1992-2007. J Viral Hepat 18 (7): e232-241.
123. Ting CT, Li WC, Chen CY, Tsai TH,. 2015. Preventive and therapeutic role of traditional Chinese herbal medicine in hepatocellular carcinoma. J Chin Med Assoc 78 (3): 139-144.
124. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A,. 2015. Global cancer statistics, 2012. CA Cancer J Clin 65 (2): 87-108.
125. Tsai JH, Hsu LS, Lin CL, et al.; 2013. 3,5,4′-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/beta-catenin signaling cascades and reversal of epithelial-mesenchymal transition. Toxicol Appl Pharmacol 272 (3): 746-756.
126. Tsukuma H, Hiyama T, Tanaka S, et al.; 1993. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328 (25): 1797-1801.
127. Viatour P, Ehmer U, Saddic LA, et al.; 2011. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway. J Exp Med 208 (10): 1963-1976.
128. Vilarinho S, Calvisi DF,. 2014. New advances in precision medicine for hepatocellular carcinoma recurrence prediction and treatment. Hepatology 60 (6): 1812-1814.
129. Villanueva A, Alsinet C, Yanger K, et al.; 2012. Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice. Gastroenterology 143 (6): 1660-1669 e1667.
130. Wang E, Bussom S, Chen J, et al.; 2011. Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment. BMC Med Genomics 4: 38.
131. Wang S, Yin J, Chen D, et al.; 2013a. Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction. Nat Chem Biol 9 (9): 579-585.
132. Wang Y, Han C, Lu L, Magliato S, Wu T,. 2013b. Hedgehog signaling pathway regulates autophagy in human hepatocellular carcinoma cells. Hepatology 58 (3): 995-1010.
133. Wang Z, Li J, Ji Y, An P, Zhang S, Li Z,. 2013c. Traditional herbal medicine: a review of potential of inhibitory hepatocellular carcinoma in basic research and clinical trial. Evid Based Complement Alternat Med 2013: 268963.
134. Wang N, Feng Y, Tan HY, et al.; 2015a. Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma. J Ethnopharmacol 164: 309-318.
135. Wang YF, Li T, Tang ZH, et al.; 2015b. Baicalein triggers autophagy and inhibits the protein kinase B/mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells. Phytother Res 29 (5): 674-679.
136. Wei W, Chua MS, Grepper S, So SK,. 2009. Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells. Mol Cancer 8: 76.
137. Wei W, Chua MS, Grepper S, So S,. 2010. Small molecule antagonists of Tcf4/beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo. Int J Cancer 126 (10): 2426-2436.
138. Wei W, Chua MS, Grepper S, So SK,. 2011. Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin. Mol Cancer 10: 16.
139. Wend P, Fang L, Zhu Q, et al.; 2013. Wnt/beta-catenin signalling induces MLL to create epigenetic changes in salivary gland tumours. EMBO J 32 (14): 1977-1989.
140. Wogan GN,. 1999. Aflatoxin as a human carcinogen. Hepatology 30 (2): 573-575.
141. Xie C, Li X, Wu J, et al.; 2015. Anti-inflammatory activity of magnesium isoglycyrrhizinate through inhibition of phospholipase A2/arachidonic acid pathway. Inflammation 38 (4): 1639-1648.
142. Yen Y, So S, Rose M, et al.; 2009. Phase I/II study of PHY906/capecitabine in advanced hepatocellular carcinoma. Anticancer Res 29 (10): 4083-4092.
143. Yu Y, Lang Q, Chen Z, et al.; 2009a. The efficacy for unresectable hepatocellular carcinoma may be improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula: a retrospective study. Cancer 115 (22): 5132-5138.
144. Yu Y, Lang QB, Chen Z, et al.; 2009b. Prognostic analysis of transarterial chemoembolization combined with a traditional Chinese herbal medicine formula for treatment of unresectable hepatocellular carcinoma. Chin Med J (Engl) 122 (17): 1990-1995.
145. Zhai XF, Chen Z, Li B, et al.; 2013. Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial. J Integr Med 11 (2): 90-100.
146. Zhan YP, Huang XE, Cao J, et al.; 2012. Clinical safety and efficacy of Kanglaite(R) (Coix Seed Oil) injection combined with chemotherapy in treating patients with gastric cancer. Asian Pac J Cancer Prev 13 (10): 5319-5321.
147. Zhang Y, Appleton BA, Wiesmann C, et al.; 2009. Inhibition of Wnt signaling by Dishevelled PDZ peptides. Nat Chem Biol 5 (4): 217-219.
148. Zhang S, Yang Y, Liang Z, et al.; 2013. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells. PLoS One 8 (12): e83699.
149. Zhang CZ, Wang XD, Wang HW, Cai Y, Chao LQ,. 2015a. Sorafenib inhibits liver cancer growth by decreasing mTOR, AKT, and PI3K expression. J BUON 20 (1): 218-222.
150. Zhang YM, Zhang YY, Bulbul A, Shan X, Wang XQ, Yan Q,. 2015b. Baicalin promotes embryo adhesion and implantation by upregulating fucosyltransferase IV (FUT4) via Wnt/beta-catenin signaling pathway. FEBS Lett 589 (11): 1225-1233.
151. Zheng X, Zeng W, Gai X, et al.; 2013. Role of the Hedgehog pathway in hepatocellular carcinoma (review). Oncol Rep 30 (5): 2020-2026.
152. Zheng YH, Yin LH, Grahn TH, Ye AF, Zhao YR, Zhang QY,. 2014. Anticancer effects of baicalein on hepatocellular carcinoma cells. Phytother Res 28 (9): 1342-1348.