A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs

Anti-Cancer Drugs

Volumn 20, Issue 9, 2009, Pages 757-769

  Sun, Yiyi ^a   Xun, Keli ^b   Wang, Yitao ^c   Chen, Xiuping ^c,d  

^a CHENGDU MEDICAL COLLEGE   (China)

^b People's Hospital of Binzhou   (China)

^c University of Macau   (Macao)

^d NONE   (China)

Author keywords

Apoptosis; Berberine; Cancer; Enzyme; Proliferation

Indexed keywords

ACYLTRANSFERASE; BERBINE DERIVATIVE; CASPASE; CYCLOOXYGENASE 2; CYTOCHROME C; DNA; DNA TOPOISOMERASE; REACTIVE OXYGEN METABOLITE; RNA;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER INHIBITION; CANCER RADIOTHERAPY; CHINESE HERB; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; GENE EXPRESSION; HELICOBACTER PYLORI; HEPATITIS B VIRUS; HUMAN; METASTASIS; MITOCHONDRIAL MEMBRANE POTENTIAL; MULTIDRUG RESISTANCE; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SYSTEMATIC REVIEW; TRANSCRIPTION REGULATION;

EID: 70349085370     PISSN: 09594973     EISSN: None     Source Type: Journal    
DOI: 10.1097/CAD.0b013e328330d95b     Document Type: Review

References (150)

1. Da Rocha A, Lopes R, Schwartsmann G. Natural products in anticancer therapy. Curr Opin Pharmacol 2001; 1:364-369.
2. Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res 2008; 22:999-1012.
3. Singhal KC. Anthelmintic activity of berberine hydrochloride against Syphacia obvelata in mice. Indian J Exp Biol 1976; 14:345-347.
4. Satou T, Akao N, Matsuhashi R, Koike K, Fujita K, Nikaido T. Inhibitory effect of isoquinoline alkaloids on movement of second-stage larvae of Toxocara canis. Biol Pharm Bull 2002; 25:1651-1654.
5. Kuo CL, Chi CW, Liu TY. The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett 2004; 203:127-137.
6. Franzblau SG, Cross C. Comparative in vitro antimicrobial activity of Chinese medicinal herbs. J Ethnopharmacol 1986; 15:279-288.
7. Zhang L, Yang L, Zheng X. A study of Helicobacterium pylori and prevention and treatment of chronic atrophic gastritis. J Tradit Chin Med 1997; 17:3-9.
8. Yang LQ, Singh M, Yap EH, Ng GC, Xu HX, Sim KY. In vitro response of Blastocystis hominis against traditional Chinese medicine. J Ethnopharmacol 1996; 55:35-42.
9. Mahady GB, Pendland SL, Stoia A, Chadwick LR. In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis. Phytother Res 2003; 17:217-221.
10. Romero MR, Efferth T, Serrano MA, Castano B, Macias RI, Briz O, et al. Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an 'in vitro' replicative system. Antiviral Res 2005; 68:75-83.
11. Li HL, Han T, Liu RH, Zhang C, Chen HS, Zhang WD. Alkaloids from Corydalis saxicola and their anti-hepatitis B virus activity. Chem Biodivers 2008; 5:777-783.
12. Ferreira AC, Isomoto H, Moriyama M, Fujioka T, Machado JC, Yamaoka Y. Helicobacter and gastric malignancies. Helicobacter 2008; 13 (Suppl 1): 28-34.
13. Farinati F, Cardin R, Cassaro M, Bortolami M, Nitti D, Tieppo C, et al. Helicobacter pylori, inflammation, oxidative damage and gastric cancer: a morphological, biological and molecular pathway. Eur J Cancer Prev 2008; 17:195-200.
14. Wang LC, Vass W, Gao CL, Chang KS. Amplification and enhanced expression of the c-Ki-ras2 protooncogene in human embryonal carcinomas. Cancer Res 1987; 47:4192-4198.
15. Chang KS, Gao C, Wang LC. Berberine-induced morphologic differentiation and down-regulation of c-Ki-ras2 protooncogene expression in human teratocarcinoma cells. Cancer Lett 1990; 55:103-108.
16. Chang KS. Down-regulation of c-Ki-ras2 gene expression associated with morphologic differentiation in human embryonal carcinoma cells treated with berberine. J Formos Med Assoc 1991; 90:10-14.
17. Liang KW, Yin SC, Ting CT, Lin SJ, Hsueh CM, Chen CY, et al. Berberine inhibits platelet-derived growth factor-induced growth and migration partly through an AMPK-dependent pathway in vascular smooth muscle cells. Eur J Pharmacol 2008; 590:343-354.
18. Katiyar SK, Meeran SM, Katiyar N, Akhtar S. p53 cooperates berberineinduced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. Mol Carcinog 2009; 47:24-37.
19. Shen G, Jeong WS, Hu R, Kong AN. Regulation of Nrf2, NF-kappaB, and AP-1 signaling pathways by chemopreventive agents. Antioxid Redox Signal 2005; 7:1648-1663.
20. Fukuda K, Hibiya Y, Mutoh M, Koshiji M, Akao S, Fujiwara H. Inhibition of activator protein 1 activity by berberine in human hepatoma cells. Planta Med 1999; 65:381-383. (Pubitemid 29249921)
21. Pandey MK, Sung B, Kunnumakkara AB, Sethi G, Chaturvedi MM, Aggarwal BB. Berberine modifies cysteine 179 of IkappaBalpha kinase, suppresses nuclear factor-kappaB-regulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res 2008; 68:5370-5379.
22. Mantena SK, Sharma SD, Katiyar SK. Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP. Carcinogenesis 2006; 27:2018-2027.
23. Letasiova S, Jantova S, Cipak L, Muckova M. Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells. Cancer Lett 2006; 239:254-262.
24. Wu HL, Hsu CY, Liu WH, Yung BY. Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity. Int J Cancer 1999; 81:923-929.
25. Krey AK, Hahn FE. Berberine: complex with DNA. Science 1969; 166:755-757.
26. Rungsitiyakorn A, Wilairat P, Panijpan B. On the pH dependence of binding of berberine to DNA. J Pharm Pharmacol 1981; 33:125-127.
27. Creasey WA. Biochemical effects of berberine. Biochem Pharmacol 1979; 28:1081-1084.
28. Islam MM, Suresh Kumar G. RNA targeting by small molecule alkaloids: studies on the binding of berberine and palmatine to polyribonucleotides and comparison to ethidium. J Mol Struct 2008; 875:382-391.
29. Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J. Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line. Cancer Chemother Pharmacol 2008; 61:1007-1018.
30. Xia AL, Wu HL, Li SF, Zhu SH, Zhang Y, Han QJ, et al. Study of the interactions of berberine and daunorubicin with DNA using alternating penalty trilinear decomposition algorithm combined with excitationemission matrix fluorescence data. Talanta 2007; 73:606-612.
31. Bhadra K, Maiti M, Kumar GS. Berberine-DNA complexation: new insights into the cooperative binding and energetic aspects. Biochim Biophys Acta Gen Subj 2008; 1780:1054-1061.
32. Islam MM, Pandya P, Chowdhury SR, Kumar S, Kumar GS. Binding of DNA-binding alkaloids berberine and palmatine to tRNA and comparison to ethidium: spectroscopic and molecular modeling studies. J Mol Struct 2008; 891:498-507.
33. Islam MM, Sinha R, Kumar GS. RNA binding small molecules: studies on t-RNA binding by cytotoxic plant alkaloids berberine, palmatine and the comparison to ethidium. Biophys Chem 2007; 125:508-520.
34. Tian X, Song Y, Dong H, Ye B. Interaction of anticancer herbal drug berberine with DNA immobilized on the glassy carbon electrode. Bioelectrochemistry 2008; 73:18-22.
35. Liu Z, Liu Q, Xu B, Wu J, Guo C, Zhu F, et al. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage. Mutat Res 2009; 662:75-83.
36. Weber WW, Hein DW. N-acetylation pharmacogenetics. Pharmacol Rev 1985; 37:25-79.
37. Butcher NJ, Tiang J, Minchin RF. Regulation of arylamine N-acetyltransferases. Curr Drug Metab 2008; 9:498-504.
38. Sim E, Pinter K, Mushtaq A, Upton A, Sandy J, Bhakta S, et al. Arylamine N-acetyltransferases: a pharmacogenomic approach to drug metabolism and endogenous function. Biochem Soc Trans 2003; 31:615-619.
39. Chung JG, Wu LT, Chu CB, Jan JY, Ho CC, Tsou MF, et al. Effects of berberine on arylamine N-acetyltransferase activity in human bladder tumour cells. Food Chem Toxicol 1999; 37:319-326.
40. Lin JG, Chung JG, Wu LT, Chen GW, Chang HL, Wang TF. Effects of berberine on arylamine N-acetyltransferase activity in human colon tumor cells. Am J Chin Med 1999; 27:265-275.
41. Chung JG, Chen GW, Hung CF, Lee JH, Ho CC, Ho HC, et al. Effects of berberine on arylamine N-acetyltransferase activity and 2-aminofluorene- DNA adduct formation in human leukemia cells. Am J Chin Med 2000; 28:227-238.
42. Wang DY, Yeh CC, Lee JH, Hung CF, Chung JG. Berberine inhibited arylamine N-acetyltransferase activity and gene expression and DNA adduct formation in human malignant astrocytoma (G9T/VGH) and brain glioblastoma multiforms (GBM 8401) cells. Neurochem Res 2002; 27:883-889.
43. Misra S, Hascall VC, Berger FG, Markwald RR, Ghatak S. Hyaluronan, CD44, and cyclooxygenase-2 in colon cancer. Connect Tissue Res 2008; 49:219-224.
44. Lin SS, Chung JG, Lin JP, Chuang JY, Chang WC, Wu JY, et al. Berberine inhibits arylamine N-acetyltransferase activity and gene expression in mouse leukemia L 1210 cells. Phytomedicine 2005; 12:351-358.
45. Rundhaug JE, Fischer SM. Cyclo-oxygenase-2 plays a critical role in UV-induced skin carcinogenesis. Photochem Photobiol 2008; 84:322-329.
46. Aparicio Gallego G, Diaz Prado S, Jimenez Fonseca P, Garcia Campelo R, Cassinello Espinosa J, Anton Aparicio LM. Cyclooxygenase-2 (COX-2): a molecular target in prostate cancer. Clin Transl Oncol 2007; 9:694-702.
47. Breinig M, Schirmacher P, Kern MA. Cyclooxygenase-2 (COX-2) - a therapeutic target in liver cancer? Curr Pharm Des 2007; 13:3305-3315.
48. Patel S, Chiplunkar S. Role of cyclooxygenase-2 in tumor progression and immune regulation in lung cancer. Indian J Biochem Biophys 2007; 44:419-428.
49. Sarkar FH, Adsule S, Li Y, Padhye S. Back to the future: COX-2 inhibitors for chemoprevention and cancer therapy. Mini Rev Med Chem 2007; 7:599-608.
50. Singh-Ranger G, Salhab M, Mokbel K. The role of cyclooxygenase-2 in breast cancer: review. Breast Cancer Res Treat 2008; 109:189-198. (Pubitemid 351644840)
51. Fukuda K, Hibiya Y, Mutoh M, Koshiji M, Akao S, Fujiwara H. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol 1999; 66:227-233. (Pubitemid 29307925)
52. Kuo CL, Chi CW, Liu TY. Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells. In Vivo 2005; 19:247-252.
53. Liu J, He C, Zhou K, Wang J, Kang JX. Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells. Biochem Biophys Res Commun 2009; 378:174-178.
54. Seaver B, Smith JR. Inhibition of COX isoforms by nutraceuticals. J Herb Pharmacother 2004; 4:11-18.
55. Shay JW, Keith WN. Targeting telomerase for cancer therapeutics. Br J Cancer 2008; 98:677-683.
56. Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer 2008; 8:167-179.
57. Biao L, Qihou W, Jin L, Shiqing H, Bing H. Study the ef fect of berber ine on the telomerase activity of human nasopharyngeal carcinoma (NPC) CNE-2. Shanxi Med J 2007; 36:1281-1283.
58. Sriwilaijareon N, Petmitr S, Mutirangura A, Ponglikitmongkol M, Wilairat P. Stage specificity of Plasmodium falciparum telomerase and its inhibition by berberine. Parasitol Int 2002; 51:99-103.
59. Makhey D, Gatto B, Yu C, Liu A, Liu LF, LaVoie EJ. Coralyne and related compounds as mammalian topoisomerase I and topoisomerase II poisons. Bioorg Med Chem 1996; 4:781-791. (Pubitemid 26202376)
60. Kim SA, Kwon Y, Kim JH, Muller MT, Chung IK. Induction of topoisomerase II-mediated DNA cleavage by a protoberberine alkaloid, berberrubine. Biochemistry 1998; 37:16316-16324.
61. Mantena SK, Sharma SD, Katiyar SK. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol Cancer Ther 2006; 5:296-308.
62. Kettmann V, Kost'alova D, Holtje HD. Human topoisomerase I poisoning: docking protoberberines into a structure-based binding site model. J Comput Aided Mol Des 2004; 18:785-796.
63. Kobayashi Y, Yamashita Y, Fujii N, Takaboshi K, Kawakami T, Kawamura M, et al. Inhibitors of DNA topoisomerase I and II isolated from the Coptis rhizomes. Planta Med 1995; 61:414-418.
64. Wang LK, Rogers BD, Hecht SM. Inhibition of topoisomerase I function by coralyne and 5, 6-dihydrocoralyne. Chem Res Toxicol 1996; 9:75-83.
65. Li TK, Bathory E, LaVoie EJ, Srinivasan AR, Olson WK, Sauers RR, et al. Human topoisomerase I poisoning by protoberberines: potential roles for both drug-DNA and drug-enzyme interactions. Biochemistry 2000; 39:7107-7116.
66. Kang MR, Chung IK. Down-regulation of DNA topoisomerase IIalpha in human colorectal carcinoma cells resistant to a protoberberine alkaloid, berberrubine. Mol Pharmacol 2002; 61:879-884.
67. Qin Y, Pang JY, Chen WH, Zhao ZZ, Liu L, Jiang ZH. Inhibition of DNA topoisomerase I by natural and synthetic mono-and dimeric protoberberine alkaloids. Chem Biodivers 2007; 4:481-487.
68. Jantova S, Cipak L, Cernakova M, Kost'alova D. Effect of berberine on proliferation, cell cycle and apoptosis in HeLa and L1210 cells. J Pharm Pharmacol 2003; 55:1143-1149.
69. Jantova S, Cipak L, Letasiova S. Berberine induces apoptosis through a mitochondrial/ caspase pathway in human promonocytic U937 cells. Toxicol In Vitro 2007; 21:25-31.
70. Lin JP, Yang JS, Lee JH, Hsieh WT, Chung JG. Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line. World J Gastroenterol 2006; 12:21-28.
71. Wang XN, Han X, Xu LN, Yin LH, Xu YW, Qi Y, et al. Enhancement of apoptosis of human hepatocellular carcinoma SMMC-7721 cells through synergy of berberine and evodiamine. Phytomedicine 2008; 15:1062-1068.
72. Kim JB, Ko E, Han W, Shin I, Park SY, Noh DY. Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells. Planta Med 2008; 74:1693-1700.
73. Lin S, Tsai SC, Lee CC, Wang BW, Liou JY, Shyu KG. Berberine inhibits HIF-1alpha expression via enhanced proteolysis. Mol Pharmacol 2004; 66:612-619.
74. Lin TH, Kuo HC, Chou FP, Lu FJ. Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide. BMC Cancer 2008; 8:58.
75. Lee S, Lim HJ, Park HY, Lee KS, Park JH, Jang Y. Berberine inhibits rat vascular smooth muscle cell proliferation and migration in vitro and improves neointima formation after balloon injury in vivo. Berberine improves neointima formation in a rat model. Atherosclerosis 2006; 186:29-37.
76. Kim S, Kim Y, Kim JE, Cho KH, Chung JH. Berberine inhibits TPA-induced MMP-9 and IL-6 expression in normal human keratinocytes. Phytomedicine 2008; 15:340-347.
77. Letasiova S, Jantova S, Muckova M, Theiszova M. Antiproliferative activity of berberine in vitro and in vivo. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005; 149:461-463.
78. Li H, Guo L, Jie S, Liu W, Zhu J, Du W, et al. Berberine inhibits SDF-1-induced AML cells and leukemic stem cells migration via regulation of SDF-1 level in bone marrow stromal cells. Biomed Pharmacother 2008; 62:573-578.
79. Yount G, Qian Y, Moore D, Basila D, West J, Aldape K, et al. Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro. J Exp Ther Oncol 2004; 4:137-143.
80. Issat T, Jakobisiak M, Golab J. Berberine, a natural cholesterol reducing product, exerts antitumor cytostatic/cytotoxic effects independently from the mevalonate pathway. Oncol Rep 2006; 16:1273-1276.
81. Szeto S, Yow CMN, Fung KW. Characterization of berberine on human cancer cells in culture. Turk J Med Sci 2002; 32:363-368.
82. Letasiova S, Jantova S, Miko M, Ovadekova R, Horvathova M. Effect of berberine on proliferation, biosynthesis of macromolecules, cell cycle and induction of intercalation with DNA, dsDNA damage and apoptosis in Ehrlich ascites carcinoma cells. J Pharm Pharmacol 2006; 58:263-270.
83. Chi CW, Chang YF, Chao TW, Chiang SH, P'Eng FK, Lui WY, et al. Flowcytometric analysis of the effect of berberine on the expression of glucocorticoid receptors in human hepatoma HepG2 cells. Life Sci 1994; 54:2099-2107.
84. Hwang JM, Wang CJ, Chou FP, Tseng TH, Hsieh YS, Lin WL, et al. Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat liver. Arch Toxicol 2002; 76:664-670.
85. Peng PL, Hsieh YS, Wang CJ, Hsu JL, Chou FP. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Toxicol Appl Pharmacol 2006; 214:8-15.
86. Mitani N, Murakami K, Yamaura T, Ikeda T, Saiki I. Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma. Cancer Lett 2001; 165:35-42.
87. Iizuka N, Miyamoto K, Okita K, Tangoku A, Hayashi H, Yosino S, et al. Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Lett 2000; 148:19-25.
88. Wu SN, Yu HS, Jan CR, Li HF, Yu CL. Inhibitory effects of berberine on Voltage-and calcium-activated potassium currents in human myeloma cells. Life Sci 1998; 62:2283-2294.
89. Tan YL, Goh D, Ong ES. Investigation of differentially expressed proteins due to the inhibitory effects of berberine in human liver cancer cell line HepG2. Mol Biosyst 2006; 2:250-258.
90. Pereira GC, Branco AF, Matos JA, Pereira SL, Parke D, Perkins EL, et al. Mitochondrially targeted effects of berberine [Natural Yellow 18, 5, 6-dihydro-9, 10-dimethoxybenzo(g)-1, 3-benzodioxolo(5, 6-a) quinolizinium] on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions. J Pharmacol Exp Ther 2007; 323:636-649.
91. Jantova S, Letasiova S, Brezova V, Cipak L, Labaj J. Photochemical and phototoxic activity of berberine on murine fibroblast NIH-3T3 and Ehrlich ascites carcinoma cells. J Photochem Photobiol B 2006; 85:163-176.
92. Orfila L, Rodriguez M, Colman T, Hasegawa M, Merentes E, Arvelo F. Structural modification of berberine alkaloids in relation to cytotoxic activity in vitro. J Ethnopharmacol 2000; 71:449-456.
93. Ko WH, Yao XQ, Lau CW, Law WI, Chen ZY, Kwok W, et al. Vasorelaxant and antiproliferative effects of berberine. Eur J Pharmacol 2000; 399:187-196.
94. Lin CC, Ng LT, Hsu FF, Shieh DE, Chiang LC. Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth. Clin Exp Pharmacol Physiol 2004; 31:65-69.
95. Anis KV, Kuttan G, Kuttan R. Role of berberine as an adjuvant response modifier during tumour therapy in mice. Pharm Pharmacol Commun 1999; 5:697-700.
96. Yang IW, Chou CC, Yung BY. Dose-dependent effects of berberine on cell cycle pause and apoptosis in Balb/c 3T3 cells. Naunyn Schmiedebergs Arch Pharmacol 1996; 354:102-108.
97. Sethi ML. Enzyme inhibition VI: inhibition of reverse transcriptase activity by protoberberine alkaloids and structure-activity relationships. J Pharm Sci 1983; 72:538-541.
98. Weber HA, Zart MK, Hodges AE, Molloy HM, O'Brien BM, Moody LA, et al. Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from three commercial suppliers. J Agric Food Chem 2003; 51:7352-7358.
99. Lin CC, Lin SY, Chung JG, Lin JP, Chen GW, Kao ST. Down-regulation of cyclin B1 and up-regulation of Wee1 by berberine promotes entry of leukemia cells into the G2/M-phase of the cell cycle. Anticancer Res 2006; 26:1097-1104.
100. Lin CC, Yang JS, Chen JT, Fan S, Yu FS, Yang JL, et al. Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway. Anticancer Res 2007; 27:3371-3378.
101. Eom KS, Hong JM, Youn MJ, So HS, Park R, Kim JM, et al. Berberine induces G1 arrest and apoptosis in human glioblastoma T98G cells through mitochondrial/caspases pathway. Biol Pharm Bull 2008; 31:558-562.
102. Yokozawa T, Satoh A, Cho EJ, Kashiwada Y, Ikeshiro Y. Protective role of Coptidis Rhizoma alkaloids against peroxynitrite-induced damage to renal tubular epithelial cells. J Pharm Pharmacol 2005; 57:367-374.
103. Li XK, Motwani M, Tong W, Bornmann W, Schwartz GK. Huanglian, A chinese herbal extract, inhibits cell growth by suppressing the expression of cyclin B1 and inhibiting CDC2 kinase activity in human cancer cells. Mol Pharmacol 2000; 58:1287-1293.
104. Hsu WH, Hsieh YS, Kuo HC, Teng CY, Huang HI, Wang CJ, et al. Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/ p38MAPK and FasL. Arch Toxicol 2007; 81:719-728.
105. Bremer E, van Dam G, Kroesen BJ, de Leij L, Helfrich W. Targeted induction of apoptosis for cancer therapy: current progress and prospects. Trends Mol Med 2006; 12:382-393.
106. Kuo CL, Chou CC, Yung BY. Berberine complexes with DNA in the berberine-induced apoptosis in human leukemic HL-60 cells. Cancer Lett 1995; 93:193-200.
107. Lin CC, Kao ST, Chen GW, Ho HC, Chung JG. Apoptosis of human leukemia HL-60 cells and murine leukemia WEHI-3 cells induced by berberine through the activation of caspase-3. Anticancer Res 2006; 26:227-242.
108. Hwang JM, Kuo HC, Tseng TH, Liu JY, Chu CY. Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells. Arch Toxicol 2006; 80:62-73.
109. Piyanuch R, Sukhthankar M, Wandee G, Baek SJ. Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells. Cancer Lett 2007; 258:230-240.
110. Choi MS, Oh JH, Kim SM, Jung HY, Yoo HS, Lee YM, et al. Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells. Int J Oncol 2009; 34:1221-1230.
111. Choi MS, Yuk DY, Oh JH, Jung HY, Han SB, Moon DC, et al. Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis. Anticancer Res 2008; 28:3777-3784.
112. Lin JP, Yang JS, Chang NW, Chiu TH, Su CC, Lu KW, et al. GADD153 mediates berberine-induced apoptosis in human cervical cancer Ca ski cells. Anticancer Res 2007; 27:3379-3386.
113. Irani K. Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res 2000; 87:179-183.
114. Vavreckova C, Gawlik I, Muller K. Benzophenanthridine alkaloids of Chelidonium majus; I. Inhibition of 5-and 12-lipoxygenase by a non-redox mechanism. Planta Med 1996; 62:397-401.
115. Hsieh YS, Kuo WH, Lin TW, Chang HR, Lin TH, Chen PN, et al. Protective effects of berberine against low-density lipoprotein (LDL) oxidation and oxidized LDL-induced cytotoxicity on endothelial cells. J Agric Food Chem 2007; 55:10437-10445.
116. Liu W, Liu P, Tao S, Deng Y, Li X, Lan T, et al. Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. Arch Biochem Biophys 2008; 475:128-134.
117. Tan Y, Tang Q, Hu BR, Xiang JZ. Antioxidant properties of berberine on cultured rabbit corpus cavernosum smooth muscle cells injured by hydrogen peroxide. Acta Pharmacol Sin 2007; 28:1914-1918.
118. Yokozawa T, Ishida A, Kashiwada Y, Cho EJ, Kim HY, Ikeshiro Y. Coptidis Rhizoma: protective effects against peroxynitrite-induced oxidative damage and elucidation of its active components. J Pharm Pharmacol 2004; 56:547-556.
119. Liu WH, Hei ZQ, Nie H, Tang FT, Huang HQ, Li XJ, et al. Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase. Chin Med J (Engl) 2008; 121:706-712.
120. Jang MH, Kim HY, Kang KS, Yokozawa T, Park JH. Hydroxyl radical scavenging activities of isoquinoline alkaloids isolated from Coptis Chinensis. Arch Pharm Res 2009; 32:341-345.
121. Meeran SM, Katiyar S, Katiyar SK. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol Appl Pharmacol 2008; 229:33-43.
122. Enk R, Ehehalt R, Graham JE, Bierhaus A, Remppis A, Greten HJ. Differential effect of Rhizoma coptidis and its main alkaloid compound berberine on TNF-alpha induced NFkappaB translocation in human keratinocytes. J Ethnopharmacol 2007; 109:170-175.
123. Lee CH, Chen JC, Hsiang CY, Wu SL, Wu HC, Ho TY. Berberine suppresses inflammatory agents-induced interleukin-1beta and tumor necrosis factor-alpha productions via the inhibition of IkappaB degradation in human lung cells. Pharmacol Res 2007; 56:193-201.
124. Hu JP, Nishishita K, Sakai E, Yoshida H, Kato Y, Tsukuba T, et al. Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways. Eur J Pharmacol 2008; 580:70-79.
125. Wartenberg M, Budde P, De Marees M, Grunheck F, Tsang SY, Huang Y, et al. Inhibition of tumor-induced angiogenesis and matrixmetalloproteinase expression in confrontation cultures of embryoid bodies and tumor spheroids by plant ingredients used in traditional chinese medicine. Lab Invest 2003; 83:87-98.
126. Lin JP, Yang JS, Wu CC, Lin SS, Hsieh WT, Lin ML, et al. Berberine induced down-regulation of matrix metalloproteinase-1, -2 and -9 in human gastric cancer cells (SNU-5) in vitro. In Vivo 2008; 22:223-230.
127. Kim S, Chung JH. Berberine prevents UV-induced MMP-1 and reduction of type I procollagen expression in human dermal fibroblasts. Phytomedicine 2008; 15:749-753.
128. Matsuo M, Sakurai H, Koizumi K, Saiki I. Curcumin inhibits the formation of capillary-like tubes by rat lymphatic endothelial cells. Cancer Lett 2007; 251:288-295.
129. Ho YT, Yang JS, Li TC, Lin JJ, Lin JG, Lai KC, et al. Berberine suppresses in vitro migration and invasion of human Scc-4 tongue squamous cancer cells through the inhibitions of Fak, Ikk, Nf-Kappab, U-Pa and Mmp-2 and -9. Cancer Lett 2009; 279:155-162.
130. Liu SJ, Sun YM, Tian DF, He YC, Zeng L, He Y, et al. Downregulated NM23-H1 expression is associated with intracranial invasion of nasopharyngeal carcinoma. Br J Cancer 2008; 98:363-369.
131. Yoshino H, Endo Y, Watanabe Y, Sasaki T. Significance of plasminogen activator inhibitor 2 as a prognostic marker in primary lung cancer: association of decreased plasminogen activator inhibitor 2 with lymph node metastasis. Br J Cancer 1998; 78:833-839.
132. Ichiki K, Mitani N, Doki Y, Hara H, Misaki T, Saiki I. Regulation of activator protein-1 activity in the mediastinal lymph node metastasis of lung cancer. Clin Exp Metastasis 2000; 18:539-545.
133. Sharom FJ. ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics 2008; 9:105-127.
134. Velamakanni S, Wei SL, Janvilisri T, van Veen HW. ABCG transporters: structure, substrate specificities and physiological roles: a brief overview. J Bioenerg Biomembr 2007; 39:465-471.
135. Sakai K, Shitan N, Sato F, Ueda K, Yazaki K. Characterization of berberine transport into Coptis japonica cells and the involvement of ABC protein. J Exp Bot 2002; 53:1879-1886.
136. Lin HL, Liu TY, Wu CW, Chi CW. Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel. Br J Cancer 1999; 81:416-422.
137. Lin HL, Liu TY, Lui WY, Chi CW. Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells. Cancer 1999; 85:1937-1942.
138. Shvarev IF, Tsetlin AL. Anti-blastic properties of berberine and its derivatives. Farmakol Toksikol 1972; 35:73-75.
139. Hoshi A, Ikekawa T, Ikeda Y, Shirakawa S, Iigo M. Antitumor activity of berberrubine derivatives. Gann 1976; 67:321-325.
140. Nishino H, Kitagawa K, Fujiki H, Iwashima A. Berberine sulfate inhibits tumor-promoting activity of teleocidin in two-stage carcinogenesis on mouse skin. Oncology 1986; 43:131-134.
141. Anis KV, Rajeshkumar NV, Kuttan R. Inhibition of chemical carcinogenesis by berberine in rats and mice. J Pharm Pharmacol 2001; 53:763-768.
142. Zhang RX, Dougherty DV, Rosenblum ML. Laboratory studies of berberine used alone and in combination with 1, 3-bis(2-chloroethyl)-1-nitrosourea to treat malignant brain tumors. Chin Med J (Engl) 1990; 103:658-665.
143. Jagetia GC, Baliga MS. Effect of Alstonia scholaris in enhancing the anticancer activity of berberine in the Ehrlich ascites carcinoma-bearing mice. J Med Food 2004; 7:235-244.
144. Peng PL, Kuo WH, Tseng HC, Chou FP. Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death. Int J Radiat Oncol Biol Phys 2008; 70:529-542.
145. Fukutake M, Yokota S, Kawamura H, Iizuka A, Amagaya S, Fukuda K, et al. Inhibitory effect of Coptidis Rhizoma and Scutellariae Radix on azoxymethane-induced aberrant crypt foci formation in rat colon. Biol Pharm Bull 1998; 21:814-817.
146. Thirupurasundari CJ, Padmini R, Devaraj SN. Effect of berberine on the antioxidant status, ultrastructural modifications and protein bound carbohydrates in azoxymethane-induced colon cancer in rats. Chem Biol Interact 2009; 177:190-195.
147. Iizuka N, Miyamoto K, Hazama S, Yoshino S, Yoshimura K, Okita K, et al. Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6. Cancer Lett 2000; 158:35-41.
148. Iizuka N, Hazama S, Yoshimura K, Yoshino S, Tangoku A, Miyamoto K, et al. Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma. Int J Cancer 2002; 99:286-291.
149. Ho YT, Yang JS, Lu CC, Chiang JH, Li TC, Lin JJ, et al. Berberine inhibits human tongue squamous carcinoma cancer tumor growth in a murine xenograft model. Phytomedicine 2009; 16:887-890.
150. Harikumar KB, Kuttan G, Kuttan R. Inhibition of progression of erythroleukemia induced by Friend virus in Balb/C mice by natural products-berberine, curcumin and picroliv. J Exp Ther Oncol 2008; 7:275-284.