Target-oriented mechanisms of novel herbal therapeutics in the chemotherapy of gastrointestinal cancer and inflammation

Current Pharmaceutical Design

Volumn 19, Issue 1, 2013, Pages 48-66

  Ko, Joshua K ^a   Auyeung, Kathy K ^a  

^a HONG KONG BAPTIST UNIVERSITY   (Hong Kong)

Author keywords

Anti inflammation; Chemotherapy; Colon cancer; Herbal therapeutics; Molecular targets; Phytochemicals

Indexed keywords

ANTHRAQUINONE DERIVATIVE; BERBERINE; CELL PROTEIN; COPTISINE; DIOSGENIN; EPIGALLOCATECHIN GALLATE; GENISTEIN; GERANYLGERANIOL; HERBACEOUS AGENT; HESPERIDIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; ISOLIQUIRITIGENIN; MAGNOLOL; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; ORIDONIN; PHOSPHATIDYLINOSITOL 3 KINASE; PLANT MEDICINAL PRODUCT; POLYPHENOL; PROTEIN KINASE B; PROTEIN NAG 1; SAPONIN; SILIBININ; TERPENOID DERIVATIVE; THYMOQUINONE; UNCLASSIFIED DRUG; VINCA ALKALOID;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER CELL; CANCER CHEMOTHERAPY; CANCER PATIENT; CARCINOGENESIS; CELL PROLIFERATION; CELL SURVIVAL; COLON CANCER; DIGESTIVE SYSTEM CANCER; ENTERITIS; HERBAL MEDICINE; HUMAN; HUMAN CELL; METASTASIS; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

EID: 84873954423     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811306010048     Document Type: Review

References (295)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127(12): 2893-917.
2. Willett WC. Diet, nutrition, and avoidable cancer. Environ Health Perspect 1995; 103 (Suppl. 8): 165-70.
3. Tomatis L, Huff J, Hertz-Picciotto I, et al. Avoided and avoidable risks of cancer. Carcinogenesis 1997; 18(1): 97-105.
4. Wattenberg LW. Chemoprevention of cancer. Cancer Res 1985; 45(1): 1-8.
5. DeVita VT Jr, Chu E. A history of cancer chemotherapy. Cancer Res 2008; 68(21): 8643-53.
6. Shrikant P, Lee K. Introduction to immunology at Roswell Park Cancer Institute. Immunol Res 2010; 46(1-3): 1-3.
7. Lin SY, Liu JD, Chang HC, Yeh, SD, Lin CH, Lee WS. Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. J Cell Biochem 2002; 84: 532-44.
8. Baek SJ, Kim JS, Jackson FR, Eling TE, McEntee MF, Lee SH. Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells. Carcinogenesis 2004; 25: 2425-32.
9. Ellington AA, Berhow MA, Singletary KW. Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins. Carcinogenesis 2005; 26: 159-67.
10. Kang JX, Liu J, Wang J, He C, Li FP. The extract of huanglian, a medicinal herb, induces cell growth arrest and apoptosis by upregulation of interferon-beta and TNF-alpha in human breast cancer cells. Carcinogenesis 2005; 26: 1934-9.
11. Ko JKS, Leung, WC, Ho WK, Chiu P. Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene. Eur J Pharmacol 2007; 559: 1-13.
12. McCarty MF. Current prospects for controlling cancer growth with non-cytotoxic agents-nutrients, phytochemicals, herbal extracts, and available drugs. Med Hypoth 2001; 56: 137-54.
13. Chin YW, Balunas MJ, Chai HB, Kinghorn AD. Drug discovery from natural sources. AAPS J 2006; 8(2): E239-53.
14. van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R. The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem 2004; 11(5): 607-28.
15. Shishodia S, Sethi G, Konopleva M, Andreeff M, Aggarwal BB. A synthetic triterpenoid, CDDO-Me, inhibits IssBBBBkinase and enhances apoptosis induced by TNF and chemotherapeutic agents through down-regulation of expression of nuclear factor ttBregulated gene products in human leukemia cells. Clin Cancer Res 2006; 12: 1828-38.
16. Tin MMY, Cho CH, Chan K, James AE, Ko JKS. Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis 2007; 28(6): 1347-55.
17. Auyeung, KKW, Liu P, Chan C, Wu W, Lee SS, Ko JKS. Herbal isoprenols induce apoptosis in human colon cancer cells through transcriptional activation of PPARtt. Cancer Invest 2008; 26: 708-17.
18. Surh Y. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003; 3: 768-80.
19. Willett WC. Diet and health: What should we eat? Science 1994; 264(5158): 532-7.
20. Pierini R, Gee JM, Belshaw NJ, Johnson IT. Flavonoids and intestinal cancers. Br J Nutr 2008; 99 (Suppl 1): ES53-9.
21. Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 2004; 134(12 Suppl): 3479S-85S.
22. Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem 2002; 50(25): 7449-54.
23. Eberhardt MV, Lee CY, Liu RH. Antioxidant activity of fresh apples. Nature 2000; 405(6789): 903-4.
24. Scott EN, Gescher AJ, Steward WP, Brown K. Development of dietary phytochemical chemopreventive agents: biomarkers and choice of dose for early clinical trials. Cancer Prev Res 2009; 2(6): 525-30.
25. Kaur M, Agarwal C, Agarwal R. Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products. J Nutr 2009; 139: 1806S-12S.
26. Kaur M, Singh RP, Gu M, Agarwal R, Agarwal C. Grape seed extract inhibits in vitro and in vivo growth of human colorectal carcinoma cells. Clin Cancer Res 2006; 15: 6194-202.
27. Paul S, De Castro AJ, Lee HJ, et al. Dietary intake of pterostilbene, a constituent of blueberries, inhibits the {beta}-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats. Carcinogenesis 2010; 31: 1272-8.
28. WCRF-AICR. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington DC: World Cancer Research Fund, American Instutite of Cancer Research 2007.
29. Moiseeva EP, Manson MM. Dietary chemopreventive phytochemicals: too little or too much? Cancer Prev Res 2009; 2(7): 611-6.
30. Ricciardiello L, Bazzoli F, Fogliano V. Phytochemicals and colorectal cancer prevention-myth or reality? Nat Rev Gastroenterol Hepatol 2011; 8: 592-6.
31. Pan MH, Lai CS, Wu JC, Ho CT. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Mol Nutr Food Res 2011; 55: 32-45.
32. Lee KW, Bode AM, Dong Z. Molecular targets of phytochemicals for cancer prevention. Nat Rev Cancer 2011; 11(3): 211-8.
33. Auyeung KKW, Mok NL, Wong CM, Cho CH, Ko JKS. Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells. Int J Mol Med 2010; 26: 341-9.
34. Auyeung KKW, Cho CH, Ko JKS. A novel anticancer effect of Astragalus saponins: transcriptional activation of NSAID-activated gene. Int J Cancer 2009; 125: 1082-91.
35. Auyeung KKW, Law PC, Ko JKS. Astragalus saponins induce apoptosis via an ERK-independent NF-aaB signaling pathway in the human hepatocellular HepG2 cell line. Int J Mol Med 2009; 23: 189-96.
36. Auyeung KKW, Woo PK, Ko JKS. Astragalus saponins modulate cell invasiveness and angiogenesis in gastric cancer cells. J Ethnopharmacol 2012; 141: 635-41.
37. Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem 1995; 270(42): 24995-5000.
38. Jeong WS, Kim IW, Hu R, Kong AN. Modulatory properties of various natural chemopreventive agents on the activation of NFkappaB signaling pathway. Pharm Res 2004; 21(4): 661-70.
39. Taupin D, Podolsky DK. Mitogen-activated protein kinase activation regulates intestinal epithelial differentiation. Gastroenterology 1999; 116: 1072-80.
40. Ding Q, Wang Q, Evers BM. Alterations of MAPK activities associated with intestinal cell differentiation. Biochem Biophy Res Comm 2001; 284: 282-8.
41. Komatsu K, Buchanan FG, Katkuri S, et al. Oncogenic potential of MEK1 in rat intestinal epithelial cells is mediated via cyclooxygenase-2. Gastroenterology 2005; 129: 577-90.
42. Cowley S, Paterson H, Kemp P, Marshall CJ. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 1994; 77: 841-52.
43. L expression through a MEK-dependent pathway. J Biol Chem 2001; 276: 6320-6.
44. Pardo OE, Arcaro A, Salerno G, Raguz S, Downward J, Seckl MJ. Fibroblast growth factor-2 induces transcriptional regulation of Bcl-XL and Bcl-2 via a MEK-dependent pathway. J Biol Chem 2002; 277: 12040-6.
45. Li Y, Li X, Sarkar FH. Gene expression profiles of I3C-and DIMtreated PC3 human prostate cancer cells determined by cDNA microarray analysis. J Nutr 2003; 133(4): 1011-9.
46. Adachi S, Shimizu M, Shirakami Y, Yamauchi J, Natsume H, Matsushima-Nishiwaki R, To S, Weinstein IB, Moriwaki H, Kozawa O. (-)-Epigallocatechin gallate downregulates EGF receptor via phosphorylation at Ser1046/1047 by p38 MAPK in colon cancer cells. Carcinogenesis 2009; 30(9): 1544-52.
47. Colombo ML, Bugatti C, Mossa A, et al. Cytotoxicity evaluation of natural coptisine and synthesis of coptisine from berberine. Il Farmaco 2001; 56(5-7): 403-9.
48. Park HJ, Kim MJ, Ha E, Chung JH. Apoptotic effect of hesperidin through caspase 3 activation in human colon cancer cells, SNU-C4. Phytomedicine 2008; 15(1-2): 147-51.
49. 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(6): 1287-93.
50. Hsu WH, Hsieh YS, Kuo HC, et al. Berberine induces apoptosis in SW 620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL. Arch Toxicol 2007; 81: 719-28.
51. Hong KJ, Dunn DM, Shen CL, Pence BC. Effects of Ganoderma lucidum on apoptotic and anti-inflammatory function in HT29 human colonic carcinoma cells. Phytother Res 2004; 18: 768-70.
52. Ban JO, Yul DY, Woo KS, et al. Inhibition of cell growth and induction of apoptosis via inactivation of NF-αB by a sulfurcompound isolated from garlic in human colon cancer cells. J Pharmacol Sci 2007; 104: 374-83.
53. 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(2): 227-33.
54. Takahashi T, Takasuka N, Ligo 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(5): 448-53.
55. Hong JG, Smith TJ, Ho CT, August DA, Yang CS. Effects of purified green and black tea polyphenols on cyclooxygenase-and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues. Biochem Pharmacol 2001; 62: 1175-83.
56. Hwang JT, Ha JH, Park IJ, Lee SK, Baik HW, Kim YM, Park OJ. Apoptotic effect of EGCG in HT29 colon cancer cells via AMPK signal pathway. Cancer Lett 2007; 247: 115-21.
57. Cichewicz RH, Zhang YJ, Seeram NP, Nair MG. Inhibition of human tumor cell proliferation by novel anthraquinones from daylilies. Life Sci 2004; 74(14): 1791-9.
58. Lin SY, Liu JD, Chang HC, Yeh SD, Lin CH, Lee WS. Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. J of Cell Biochem 2001; 84(3): 532-44.
59. Gali-Muhtasib H, Diab-Assaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, Schneider-Stock R. Thymoquinone extracted from black seed triggers apoptotic cell death in huma colorectal cancer cells via a p53-dependent mechanism. Int J Oncol 2004; 25(4): 857-66.
60. Balan KV, Prince J, Han Z, et al. Antiproliferative activity induction of apotosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia. Phytomedicine 2007; 12: 263-72.
61. Zhu Y, Xie LP, Chen G, Wang HZ, Zhang RQ. Effects of oridonin on proliferation of HT29 human colon carcinoma cell lines both in vitro and in vivo in mice. Pharmazie 2007; 62(6): 439-44.
62. Raju J, Bird RP. Diosgenin, a naturally occurring furostanol saponin suppresses 3-hydroxy-3-methylglutaryl CoA reductase expression and induces apoptosis in HCT-116 human colon carcinoma cells. Cancer Lett 2007; 255: 194-204.
63. Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS. Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J Surg Res 2007; 143(1): 58-65.
64. Kim EJ, Shin HK, Park JHY. Genistein inhibits insulin-like growth factor-I receptor signaling in HT29 human colon cancer cells; a possible mechanism of the growth inhibitory effect of genistein. J Med Food 2005; 8(4): 431-8.
65. Kim HY, Yu R, Kim JS, Kim YK, Sung MK. Antiproliferative crude soy saponin extract modulates the expression of IδBα, protein kinase C, and cyclooxygenase-2 in human colon cancer cells. Cancer Lett 2004; 210: 1-6.
66. Dragsted L, Srube M, Larsen J. Cancer-protective factors in fruits and vegetables: biochemical and biological background. Pharmacol Toxicol 1993; 72(Suppl. 1): 116-35.
67. Pezzuto J. Plant-derived anticancer agents. Biochem Pharmcol 1996; 53: 121-33.
68. Crowell PL. Prevention therapy of cancer by dietary monoterpenes. J Nutr 1999; 129: 775-8.
69. Masuda Y, Nakajo S, Nakaya K, Ohizumi H, Ohsawa S, Sakai I. Geranylgeraniol is a potent inducer of apoptosis in tumor cells. J Biochem (Tokyo) 1995; 117: 11-3.
70. Favre G, Miquel K, Pradines A. Farnesol and geranylgeraniol induce actin cytoskeleton disorganization and apoptosis in A549 lung adenocarcinoma cells. Biochem Biophy Res Comm 1996; 225: 869-76.
71. Nakao K, Nakata K, Takeda Y, et al. Geranylgeraniol, an intermediate product in mevalonate pathway, induces apoptotic cell death in human hepatoma cells: Death receptor-independent activation of caspase-8 with down-regulation of Bcl-xL expression. Japan J Cancer Res 2001; 92: 918-25.
72. Emery JG, McDonnell P, Burke MB, et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273: 14363-7.
73. Bradfute DL, Simoni RD. Non-sterol compounds that regulate cholesterogenesis. Analogues of farnesyl pyrophosphate reduce 3-hydroxy-3-methylglutaryl-coenzyme A reductase levels. J Biol Chem 1994; 269: 6645-50.
74. Rao L, Perez D, White E. Lamin proteolysis facilitates nuclear events during apoptosis. J Cell Bio 1996; 135: 1441-55.
75. Clarke S. Protein isoprenylation and methylation at carboxylterminal cysteine residues. Ann Rev Biochem 1992; 61: 355-86.
76. Rao CV, Hirose Y, Cooma I, Reddy BS. Modulation of experimental colon tumorigenesis by types and amount of dietary fatty acids. Cancer Res 2001; 61: 1927-33.
77. Hall PA, Coates PJ, Ansari B, Hopwood D. Regulation of cell number in mammalian gastrointestinal tract: the importance of apoptosis. J Cell Sci 1994; 107: 3569-75.
78. Meigs TE, Roseman DS, Simoni RD. Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation by the nonsterol mevalonate metabolite Farnesol in vivo. J Biol Chem 1996; 271: 7916-22.
79. Meigs TE, Simoni RD. Farnesol as a regulator of HMG-CoA reductase degradation: characterization and role of farnesyl pyrophosphatase. Arch Biochem Biophy 1997; 345: 1-9.
80. Chakrabarti R, Engleman EG. Interrelationships between mevalonate metabolism and the mitogenic signaling pathway in T lymphocyte proliferation. J Biol Chem 1991; 266: 12216-22.
81. Voziyan PA, Goldner CM, and Melnykovych G. Farnesol inhibits phosphatidylcholine biosunthesis in cultured cells be decreasing cholinephosphotransferase activity. Biochem J 1993; 295: 757-62.
82. Burke YD, Stark MJ, Roach SL, Sen SE, Crowell PL. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids 1997; 32: 151-6.
83. Sebti SM, Hamilton AD. Inhibition of ras prenylation: A novel approach to cancer chemotherapy Pharmacol Ther 1997; 74: 103-14.
84. Coleman PS, Chen L, Sepp-Lorenzino L. Cholesterol metabolism and tumor cell proliferation. Subcell Biochem 1997; 28: 363-426.
85. Brown MS, Goldstein JL. Multivalent feedback regulation of HMG-CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res 1980; 21: 505-17.
86. Rao CV, Newmark HL, Reddy BS. Chemopreventive effect of Farnesol and lanosterol on colon carcinogenesis. Cancer Detect Prev 2002; 26: 419-25.
87. Vance DE. Phosphatidylcholine metabolism: masochistic enzymology, metabolic regulation, and lipoprotein assembly. Biochem Cell Biol 1990; 68: 1151-65.
88. Jackowski S. Coordination of membrane phospholipid synthesis with the cell cycle. J Biol Chem 1994; 269: 3858-67.
89. Cui Z, Houweling M, Chen MH, et al. A genetic defect in phosphatidylcholine biosynthesis triggers apoptosis in Chinese hamster ovary cells. J Biol Chem 1996; 271: 14668-71.
90. Jackowski S. Cell cycle regulation of membrane phospholipid metabolism. J Biol Chem 1996; 271: 20219-22.
91. Anthony ML, Zhao M, Brindle KM. Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells. J Biol Chem 1999; 274: 19686-92.
92. Miquel K, Pradines A, Terce' F, Selmi S, Favre G. Competitive inhibition of choline phosphotransferase by geranylgeraniol and farnesol inhibits phosphatidylcholine synthesis and induces apoptosis in human lung adenocarcinoma A549 cells. J Biol Chem 1998; 273: 26179-86.
93. Staines AG, Sindelar P, Coughtrie MW, Burchell B. Farnesol is glucuronidated in human Liver. Biochem J 2004; 384(Pt 3): 637-45.
94. Roullet J, Xue H, Chapman J, et al. Farnesyl analogues inhibit vasoconstriction in animal and human arteries. J Clin Invest 1996; 97: 2384-90.
95. 2+ channels in vascular smooth muscle cells. J Biol Chem 1997; 272: 32240-46.
96. Parekh HS, Liu G, Wei MQ. A new dawn for the use of traditional Chinese medicine in cancer therapy. Mol Cancer 2009; 8: 21.
97. Wang S, Penchala S, Prabhu S, Wang J, Huang Y. Molecular basis of traditional Chinese medicine in cancer chemoprevention. Curr Drug Dis Tech 2010; 7: 67-75.
98. Kim JH, Park JS, Chae BS, Kang TW, Park CB, Ahn YK. Immunobiological studies on doses of methanol extract of Astragali Radix. Yakhak Hoechi 1996; 40(3): 326-34.
99. Lee SJ, Oh SG, Seo SW, et al. Oral administration of Astragalus membranaceus inhibits the development of DNFB-induced dermatitis in NC/Nga mice. Biol Pharm Bull 2007; 30(8): 1468-71.
100. Kajimura K, Takagi Y, Miyano K, et al. Polysaccharide of Astragali Radix enhance IgM antibody production in aged mice. Biol Pharm Bull 1997; 20(11): 1178-82.
101. Kang H, Ahn KS, Cho CW, Bae HS. Immunomodulatory effect of Astragali Radix extract on murine Th1/Th2 cell lineage development. Biol Pharm Bull 2004; 27(12): 1946-50.
102. Kurashige S, Akuzawa Y, Endo F. Effects of Astragali Radix extract on carcinogenesis, cytokine production, and cytotoxicity in mice treated with a carcinogen, N-butyl-N'-butanolnitrosoamine. Cancer Invest 1999; 17(1): 30-5.
103. Chen XJ, Bian ZP, Lu S, et al. Cardiac protective effect of Astragalus on viral myocarditis mice: comparison with perindopril. Am J Chin Med 2006; 34(3): 493-502.
104. Xu XL, Ji H, Gu SY, Shao Q, Huang QJ, Cheng YP. Modification of alterations in cardiac function and sarcoplasmic reticulum by astragaloside IV in myocardial injury in vivo. Eur J Pharmacol 2007; 568(1-3): 203-12.
105. Wu XL, Wang YY, Cheng J, Zhao YY. Calcium channel blocking activity of calycosin, a major active component of Astragali Radix, on rat aorta. Acta Pharmacol Sin 2006; 27(8): 1007-12.
106. Lee SH, Lee CW, Lee JW, et al. Induction of apoptotic cell death by 2'-hydroxycinnamaldehyde is involved with ERK-dependent inactivation of NF-δB in TNF-α treated SW620 colon cancer cells. Biochem Pharmacol 2005; 70: 1147-57.
107. Zhang YW, Wu CY, Cheng JT. Merit of Astragalus polysaccharide in the improvement of early diabetic nephropathy with an effect on mRNA expressions of NF-δB and IδB in renal cortex of streptozotoxin-induced diabetic rats. J Ethnopharmacol 2007; 114(3): 387-92.
108. Keiji K, Yasuhiro T, Noboru U, et al. Protective effect of Astragali Radix against Japanese encephalitis virus infection in mice. Biol Pharm Bull 1996; 19(9): 1166-9.
109. Xu F, Zhang Y, Xiao SY, et al. Absorption and metabolism of Astragali Radix decoction: in silico, in vitro, and a case study in vivo. Drug Metabol Dis. 2006; 34(6): 913-24.
110. Yu QT, Qi LW, Li P, Yi L, Zhao J, Bi ZM. Determination of seventeen main flavonoids and saponins in the medicinal plant Huangqi (Radix Astragali) by HPLC-DAD-ELSD. J Sep Sci 2007; 30: 1292-9.
111. Kitagawa I, Wang HK, Saito M, Takagi A, Yoshikawa M. Saponin and sapogenol. XXXV. Chemical constituents of Astragali Radix, the root of Astragalus membranaceus Bunge. (2). Astragalosides I, II and IV, acetylastragaloside I and isoastragalosides I and II. Chem Pharm Bull 1983; 31(2): 698-708.
112. Ma XQ, Shi Q, Duan JA, Dong TTX, Tsim WK. Chemical analysis of Radix Astragali (Huangqi) in China: a comparison with its adul terants and seasonal variations. J Agri Food Chem 2002; 50(17): 4861-6.
113. McKenna DJ, Hughes K, Jones K. Astragalus. Int J Integr Med 2002; 4: 40-6.
114. He Z-Q, Findlay JA. Constituents of Astragalus membranaceus. J Nat Prod 1991; 54: 810-5.
115. Lin LZ, He XG, Lindenmaier M. Liquid chromatographyelectrospray ionization mass spectrometry study of the flavoniods of the roots of Astrgalus mongholicus and A. membranaceus. J Chromatogr A 2000; 876: 87-95.
116. Bedir E, Pugh B, Calis I, Pasco DS, Khan IA. Immunostimulatory effects of cycloartane-type triterpene glycosides from Astragalus species. Biol Pharm Bull 2000; 23: 834-7.
117. Jiao Y, Wen J, Yu X. Influence of flavonoid of Astragalus membranaceus's stem and leave on the function of cell mediated immunity in mice. Zhongguo Zhong Xi Yi Jie He Za Zhi 1999; 19: 356-8.
118. Yu YQ, Sun WZ. Study on regulation effects of TNF-α, IL-8 and sIL-2r content to patients of ulcerative colitis by mediation method. J Harbin Univ Comm Nat Sci 2002; 18: 248-50.
119. Ko JKS, Chik CWS. The protective action of radix Astragalus membranaceus against hapten-induced colitis through modulation of cytokines. Cytokine 2009; 47: 85-90.
120. Erdem Y, Erdal B, Ihsan C, Yoshihisa T, Yasukazu O. Effects of triterpene saponins from Astragalus species on in vitro cytokine release. J Ethnopharmacol 2005; 96: 71-7.
121. Zhang WJ, Hufnagl P, Binder BR, Wojta J. Anti-inflammatory activity of astragaloside IV is mediated by inhibition of NF-δB activation and adhesion molecule expression. Thromb and Haemost 2003; 90(5): 904-14.
122. Navarrete A, Arrieta J, Terrones L, Abou-Gazar H, Calis I. Gastroprotective effect of astragaloside IV: role of prostaglandins, sulfhydryls and nitric oxide. J Pharm Pharmacol 2005; 57(8): 1059-64.
123. Yin XX, Zhang YD, Yu JX, et al. The antioxidative effects of Astragalus saponin I protect against development of early diabetic nephropathy. J Pharmacol Sci 2006; 101: 166-73.
124. Yang Q, Lu JT, Zhou AW, Bin H, He WG, Chen MZ. Antinociceptive effect of astragalosides and its mechanism of action. Acta Pharmacol Sin 2001; 22(9): 809-12.
125. Yin XX, Zhang YD, Wu HW, et al. Protective effects of Astragalus saponin I on early stage of diabetic nephropathy in rats. J Pharmacol Sci 2004; 95(2): 256-66.
126. Yu JX, Zhang YD, Sun S, et al. Inhibitory effects of astragaloside IV on diabetic peripheral neuropathy in rats. Can J Physioly Pharmacol 2006; 84(6): 579-87.
127. Gu WZ, Chen R, Brandwein S, McAlpine J, Burres N. Isolation, purification, and characterization of immunosuppressive compounds from tripterygium: triptolide and tripdiolide. Int J Immunopharmacol 1995; 17: 351-6.
128. Ma PC, Lu XY, Yang JJ and Zheng QT. 16-Hydroxytriptolide, a new active diterpene isolated from Tripterygium wilfordii. Yao Xue Xue Bao 1991; 26: 759-63.
129. Kupchan SM, Court WA, Dailey RG Jr, Gilmore CJ, Bryan RF. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J Am Chem Soc 1972; 94: 7194-5.
130. Da XM. Zhong Yao Du Li Xue (Toxicology of Chinese Herbs). Taipei: Qi Ye Publication 1989; pp 154-5.
131. Li NQ. Clinical and experimental study on shen-qi injection with chemotherapy in the treatment of malignant tumor of digestive tract. Zhongguo Zhongxiyi Jiehe Zazhi 1992; 12: 588-92.
132. Yang S, Chen J, Guo Z, et al. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther 2003; 2: 65-72.
133. Frese S, Pirnia F, Miescher D, et al. PG490-mediated sensitization of lung cancer cells to Apo2L/TRAIL-induced apoptosis requires activation of ERK2. Oncogene 2003; 22: 5427-35.
134. Yinjun L, Jie J and Yungui W. Triptolide inhibits transcription factor NF-kappaB and induces apoptosis of multiple myeloma cells. Leukemia Res 2005; 29: 99-105.
135. Shamon LA, Pezzuto JM, Graves JM. Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett 1997; 112: 113-7.
136. Kiviharju TM, Lecane PS, Sellers RG, Peehl DM. Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. Clin Cancer Res 2002; 8: 2666-74.
137. Lee KY, Chang W, Qiu D, Kao PN, Rosen GD. PG490 (triptolide) cooperates with tumor necrosis factor-alpha to induce apoptosis in tumor cells. J Biol Chem 1999; 274: 13451-5.
138. Qiu D, Zhao G, Aoki Y, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purinebox/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem 1999; 274: 13443-50.
139. Zhao G, Vaszar LT, Qiu D, Shi L and Kao PN. Anti-inflammatory effects of triptolide in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 2000; 279: L958-66.
140. Jiang XH, Wong BC, Lin MC, Zhu GH, Kung HF, Jiang SH, Yang D and Lam SK. Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-kappaB activation in gastric cancer cells. Oncogene 2001; 20: 8009-18.
141. Yu DQ, Zhang DM, Wang HB, Liang XT. Structure modification of triptolide, a diterpenoid from Tripterygium Wilfordii. Yao Xue Xue Bao 1992; 27: 830-6.
142. Chang WT, Kang JJ, Lee KY. Triptolide and chemotherapy cooperate in tumor cell apoptosis a role for the p53 pathway. J Biol Chem 2001; 276: 2221-7.
143. Duflos A, Kruczynski A, Barret JM. Novel aspects of natural and modified vinca alkaloids. Curr Med Chem 2002; 2(1): 55-70.
144. Bennouna J, Delord JP, Campone M, Nguyen L. Vinflunine: a new microtubule inhibitor agent. Clin Cancer Res 2008; 14(6): 1625-32.
145. Jordan MA, Thrower D, Wilson L. Mechanism of inhibition of cell proliferation by vinca alkaloids. Cancer Res 1991; 51(8): 2212-22.
146. Per A, Bo L, Klas N. Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A. Acta Oncol 2008; 47: 293-300.
147. Huang Y, Fang Y, Wu J, et al. Regulation of Vinca alkaloidinduced apoptosis by NF-KB/IKB pathway in human tumor cells Mol Cancer Ther 2004; 3(3): 271-7.
148. Tellingen O van, Beijnen JH, Nooijen WJ, Bult A. Plasma pharmacokinetics of vinblastine and the investigational vinca alkaloid w-(deacetyl-0-4-vinblastoyl-23)-l-ethyl isoleucinate in mice as determined by high-performance liquid chromatography. Cancer Res 1993; 53: 2061-5.
149. Zhou XJ, Rahmani R. Preclinical and clinical pharmacology of Vinca alkaloids. Drugs 1992; 44: 1-16.
150. Harris AL. Angiogenesis as a new target for cancer control. Eur J Cancer Suppl 2003; 1(2): 1-12.
151. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005; 100: 72-9.
152. Tsai TH. Analytical approaches for traditional Chinese medicines exhibiting antineoplastic activity. J Chromatogr B Biomed Sci Appl 2001; 764(1-2): 27-48.
153. nd ed. Boca Raton: CRC Press 1999; pp 469-72.
154. Ribatti D, Guidolin D, Conconi MT, et al. Vinblastine inhibits the angiogenic response induced by adrenomedullin in vitro and in vivo. Oncogene 2003; 22(41): 6458-61.
155. Vacca A, Iurlaro M, Ribatti D, et al. Antiangiogenesis is produced by nontoxic doses of vinblastine. Blood 1999; 94: 4143-55.
156. Chatterjee K, Zhang J, Tao R, Honbo N, Karliner JS. Vincristine attenuates doxorubicin cardiotoxicity. Biochem Biophy Res Comm 2008; 373(4): 555-60.
157. Sharma M, Shukla S. Hypoglycaemic effect of ginger. J Res Indian Yoga Homeopathy 1977; 12: 127-130.
158. Dorso CR, Levin RI, Eldor A, Jaffe EA, Weksler BB. Chinese food and platelets. New Eng J Med 1980; 303: 756-7.
159. Shoji N, Iwasa A, Takemoto T, Ishida Y, Ohizumi Y. Cardiotonic principles of ginger. J Pharma Sci Am Pharm Assoc 1982; 71: 1174-5.
160. Mustafa T, Srivastava KC. Ginger (zingiber officinale) in migraine headache. J Ethnopharmacol 1990; 29: 267-73.
161. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther 2002; 27: 391-401.
162. Onu LI, Okafor GI. Effect of physical and chemical factor variations on the efficiency of mechanical slicing of Nigerian ginger (Zingiber Officinale Rose). J Food Eng 2002; 56: 43-7.
163. Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res 1980; 111: 259-65.
164. Kaur C, Kapoor HC. Anti-oxidant in vegetables. Int J Food Sci Tech 2002; 37: 153-61.
165. Wang Q, Zeng ZH, Chen Y. Antiactive oxygen effect of Zingiber officinale petroleum extracts with a four oxygen free radicals system. Chin Pharm J 1997; 32: 343-6.
166. Liu N, Huo G, Zhang L, Zhang X. Effect of Zingiber Officinale Rosc on lipid peroxidation in hyperlipidemia rats. Wei Sheng Yan Jiu 2003; 32: 22-3.
167. Yamahara J, Mochizuki M, Rong HQ, Matsuda H, Fujimura H. The anti-ulcer effect in rats of ginger constituents. J Ethnopharmacol 1988; 23: 299-304.
168. Al-Yahya MA, Rafatullah S, Mossa JS, Ageel AM, Parmar NS, Tariq M. Gastroprotective activity of ginger zingiber officinale rose., in albino rats. Am J Chin Med 1989; 17: 51-6.
169. Sun QW, Hou Y. Protection of ginger on gastric mucosa and its effect on gastric function in rats. Nan Yei Xue Yuan Xue Bao 1991; 11: 202-4.
170. Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407(6805): 770-6.
171. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995; 267(5203): 1456-62.
172. Debatin KM. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother 2004; 53(3): 153-9.
173. Kim R, Tanabe K, Uchida Y, Emi M, Inoue H, Toge T. Current status of the molecular mechanisms of anticancer drug-induced apoptosis. The contribution of molecular-level analysis to cancer chemotherapy. Cancer Chemother Pharmacol 2002; 50(5): 343-52.
174. Lacour S, Micheau O, Hammann A, et al. Chemotherapy enhance TNF-related apoptosis-inducing ligand DISC assembly in HT29 human colon cancer cells. Oncogene 2003; 22(12): 1807-16.
175. Barnhart BC, Alappat EC, Peter ME. The CD95 type I/type II model. Semin Immunol 2003; 15(3): 185-93.
176. Jia L, Patwari Y, Srinivasula SM, et al. Bax translocation is crucial for the sensitivity of leukaemic cells to etopside-induced apoptosis. Oncogene 2001; 20(35): 4817-26.
177. Verrier F, Deniaud A, LeBras M, et al. Dynamic evolution of the adenine nucleotide translocase interacting during chemotherapyinduced apoptosis. Oncogene 2004; 23(49): 8049-64.
178. Song Z, Yao X, Wu M. Direct interaction between survivin and Smac/Diablo is essential for the anti-apotptotic activity of survivin during taxol-induced apoptosis. J Biol Chem 2003; 278(25): 23130-40.
179. Wilkinson JC, Wilkinson AS, Scott FL, Csomos RA, Salvesen GS, Duckett CS. Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs). A caspase-independent mechanism for apoptotic inhibition. J Biol Chem 2004; 279(49): 51082-90.
180. Srinivasula SM, Datta P, Fan XJ, Fernandes-Alnemri T, Huang Z, Alnemri ES. Molecular determinants of the caspase-promoting activity of Smac/Diablo and its role in the death receptor pathway. J Biol Chem 2000; 275(46): 36152-7.
181. Sun XM, Bratton SB, Butterworth M, MacFarlane M, Cohen GM. Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/Diablo and subsequent inactivation of X-linked inhibitor-or apoptosis protein. J Biol Chem 2002; 277(13): 11345-51.
182. Hasenjager A, Gillissen B, Muller A, et al. Smac induces cytochrome c release and apoptosis independently from Bax/Bcl-x(L) in a strictly caspase-3-dependent manner in human carcinoma cells. Oncogene 2004; 23(26): 4523-35.
183. Hao Y, Sekine K, Kawabata A, et al. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol 2004; 6(9): 849-60.
184. Bartling B, Lewensohn R, Zhivotovsky B. Endogenously released Smac is insufficient to mediate cell death of human lung carcinoma in response to etoposide. Exp Cell Res 2004; 298(1): 83-95.
185. Trauth BC, Klas C, Peters AM, et al. Monoclonal antibodymediated tumor regression by induction of apoptosis. Science 1989; 245(4915): 301-5.
186. Muzio M, Stockwell BR, Stennicke HR, Salvesen GS, Dixit VM. Caspase activation: The induced-proximity model. J Biol Chem 1998; 273: 2926-30.
187. Wiley SR, Schooley K, Smolak PJ, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995; 3: 673-82.
188. Greffith TS, Rauch CT, Smolak PJ, et al. Functional analysis of TRAIL receptor using monoclonal antibodies. J Immunol 1999; 162(5): 2597-605.
189. Degli-Esposti M. To die or not to die--the question of the TRAIL receptor. J Leuko Biol 1999; 65: 535-42.
190. Walczak H, Degli-Esposti MA, Johnson RS, et al. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 1997; 16(17): 5386-97.
191. 53-regulated DNA damageinducible gene that is overexpressed in primary tumor of the gastrointestinal tract. Oncogene 1999; 18(28): 4153-9.
192. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89(2): 309-19.
193. Shi J, Zheng D, Man K, Fan S, Xu RA. TRAIL: a potential agent for cancer therapy. Curr Mol Med 2003; 3: 727-36.
194. Keane MM, Ettenberg SA, Nau MM, Russell EK, Lipkowitz S. Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. Cancer Res 1999; 59(3): 734-41.
195. Nagata S. Apoptosis by death factor. Cell 1997; 88: 355-65.
196. Wiley SR, Schooley K, Smolak PJ Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995; 3(6): 673-82.
197. Hague A, Hicks D, Hasan F, et al. Increased sensitivity to TRAILinduced apoptosis occurs during the adenoma to carcinoma transition of colorectal carcinogenesis. Br J Cancer 2005; 92: 736-42.
198. Mohr A, Henderson G, Dudus L, et al. AAV-encoded expression of TRAIL in experimental human colorectal cancer leads to tumor regression. Gene Ther 2004; 11: 534-43.
199. Sova P, Ren X, Ni S, et al. A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases. Mol Ther 2004; 9: 496-509.
200. Schleipen B, Hertrampf T, Fritzemeier KH, et al. ERα-specific agonists and genistein inhibit proliferation and induce apoptosis in the large and small intestine. Carcinogenesis 2011; 32(11): 1675-83.
201. Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Ann Rev Immunol 1996; 14: 649-83.
202. Orlowski RZ, Baldwin AS Jr. NF-kappaB as a therapeutic target in cancer. Trends Mol Med 2002; 8(8): 385-9.
203. Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002; 2(4): 301-10.
204. Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem 1995; 270(42): 24995-5000.
205. Jeong WS, Kim IW, Hu R, Kong AN. Modulatory properties of various natural chemopreventive agents on the activation of NFkappaB signaling pathway. Pharm Res 2004; 21(4): 661-70.
206. Bours V, Bonizzi G, Bentires-Alj M, et al. NF-δB activation in response to toxical and therapeutical agents: role in inflammation and caner treatment. Toxicology 2000; 153: 27-38.
207. Li QT, Verma IM. NF-δB regulation in the immune system. Nat Rev Immunol 2002; 2: 725-34.
208. Schottelius AJ, Dinter H. Cytokines, NF-δB, microenvironment, intestinal inflammation and cancer. Cancer Treat Res 2006; 120: 67-87.
209. Greten FR, Eckmann L, Greten TF, et al. IKKα links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004; 118: 285-96.
210. Matthias L, Philipp L, Josef R. Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Sem Cancer Biol 2005; 15: 277-89.
211. Zhang WJ, Hufnagl P, Binder BR, Wojta J. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression. Thromb Haemost 2003; 90(5): 904-14.
212. Tzeng E, Billiar TR, Williams DL, et al. Adenovirus-mediated inducible nitric oxide synthase gene transfer inhibits hepatocyte apoptosis. Surgery 1998; 124(2): 278-83.
213. Mannick JB, Asano K, Izumi K, Kieff E, Stamler JS. Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation, Cell 1994; 79(7): 1137-46.
214. Crowell JA, Steele VE, Sigman CC, Fay JR. Is inducible nitric oxide synthase a target for chemoprevention, Mol Cancer Ther 2003; 2(8): 815-23.
215. Taylor BS, de Vera ME, Ganster RW, et al. Multiple NF-. B enhancer elements regulate cytokine induction of the human inducible nitric oxide synthase gene. J Biol Chem 1998; 273(24): 15148-56.
216. Janssen-Heininger YM, Macara I, Mossman BT. Cooperativity between oxidants and tumor necrosis factor in the activation of nuclear factor (NF)-kappaB: requirement of Ras/mitogen-activated protein kinases in the activation of NF-kappaB by oxidants. Am J Respir Cell Mol Biol 1999; 20(5): 942-52.
217. Arsura M, Cavin LG. Nuclear factor-[B and liver carcinogenesis. Cancer Lett 2005; 229: 157-69.
218. Taupin D, Podolsky DK. Mitogen-activated protein kinase activation regulates intestinal epithelial differentiation. Gastroenterology 1999; 116: 1072-80.
219. Ding Q, Wang Q, Evers BM. Alterations of MAPK activities associated with intestinal cell differentiation. Biochem Biophy Res Comm 2001; 284: 282-8.
220. Komatsu K, Buchanan FG, Katkuri S, et al. Oncogenic potential of MEK1 in rat intestinal epithelial cells is mediated via cyclooxygenase-2. Gastroenterology 2005; 129: 577-90.
221. Cowley S, Paterson H, Kemp P, Marshall CJ. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 1994; 77: 841-52.
222. Jost M, Huggett TM, Kari C, Boise LH, Rodeck U. Epidermal growth factor receptor-dependent control of keratinocyte survival and Bcl-XL expression through a MEK-dependent pathway. J Biol Chem 2001; 276: 6320-6.
223. Pardo OE, Arcaro A, Salerno G, Raguz S, Downward J, Seckl MJ. Fibroblast growth factor-2 induces transcriptional regulation of Bcl-XL and Bcl-2 via a MEK-dependent pathway. J Biol Chem 2002; 277: 12040-6.
224. Li Y, Li X, Sarkar FH. Gene expression profiles of I3C-and DIMtreated PC3 human prostate cancer cells determined by cDNA microarray analysis. J Nutr 2003; 133(4): 1011-9.
225. Adachi S, Shimizu M, Shirakami Y, et al. (-)-Epigallocatechin gallate downregulates EGF receptor via phosphorylation at Ser1046/1047 by p38 MAPK in colon cancer cells. Carcinogenesis 2009; 30(9): 1544-52.
226. Chen C, Shen G, Hebbar V, Hu R, Owuor ED, Kong AN. Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells. Carcinogenesis 2003; 24(8): 1369-78.
227. Jiang BH, Jiang GQ, Zheng JZ, Lu ZM, Hunter T, Vogt PK. Phosphatidylinositol 3-kinase signaling controls levels of hypoxiainducible factor. Cell Growth Differ 2001; 12: 363-9.
228. Zhong H, Chiles K, Feldser D, et al. Modulation of hypoxiainducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 2000; 60: 1541-5.
229. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2002; 2: 489-501.
230. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005; 4: 988-1004.
231. Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci 2001; 114(13): 2375-82.
232. Wang QD, Wang XF, Hernandez A, Hellmich MR, Gatalica Z, Evers BM. Regulation of TRAIL expression by the phosphatidylinositol 3-kinase/AKT/GSK-3 pathway in human colon cancer cells. J Biol Chem 2002; 277(39): 36602-10.
233. Segrelles C, Ruiz S, Santos M, et al. AKT mediates an angiogenic switch in transformed keratinocytes. Carcinogenesis 2004; 25(7): 1137-47.
234. Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004; 4: 335-48.
235. Philp AJ, Campbell IG, Leet C, et al. The phosphatidylinositol 3'-kinase p85α gene is an oncogene in human ovarian and colon tumors. Cancer Res 2001; 61: 7426-9.
236. Hudson CC, Liu M, Chiang GG, et al. Regulation of hypoxiainducible factor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol 2002; 22(20): 7004-14.
237. Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 2006; 5: 671-88.
238. Cheng JQ, Lindsley CW, Cheng GZ, Yang H, Nicosia SV. The AKT/PKB pathway: molecular target for cancer drug discovery. Oncogene 2005; 24: 7482-92.
239. Luo J, Manning BD, Cantley LC. Targeting the PI3K-AKT pathway in human cancer: Rationale and promise. Cancer Cell 2003; 4: 257-62.
240. Inoki K, Ouyang H, Li Y, Guan KL. Signaling by target of rapamycin proteins in cell growth control. Microbiol. Mol Biol Rev 2005; 69: 79-100.
241. Qi W, Weber CR, Wasland K, Savkovic SD. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. BMC Cancer 2011; 11: 219.
242. Walker EH, Pacold ME, Perisic O, et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 2000; 6(4): 909-19.
243. Phillips PA, Sangwan V, Borja-Cacho D, et al. Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett 2011; 308(2): 181-8.
244. Baek SJ, Horowitz JM, Eling TE. Molecular cloning and characterization of human nonsteroidal anti-inflammatory drug-activated gene promoter. Basal transcription is mediated by Sp1 and Sp3. J Biol Chem 2001; 276: 33384-92.
245. Jang TJ, Kang HJ, Kim JR, Yang CH. Non-steroidal antiinflammatory drug activated gene (NAG-1) expression is closely related to death receptor-4 and-5 induction, which may explain sulindac sulfide induced gastric cancer cell apoptosis. Carcinogenesis 25: 1853-8.
246. Bootcov MR, Bauskin AR, Valenzuela SM, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci USA 1997; 94: 11514-9.
247. Yang H, Filipovic Z, Brown D, Breit SN, Vassilev LT. Macrophage inhibitory cytokine-1: a novel biomarker for p53 pathway activation. Mol Cancer Ther 2003; 2: 1023-9.
248. Baek SJ, Wilson LC, His LC, Eling TE. Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, selectively induces the early growth response-1 gene independently of PPAR gamma. A novel mechanism for its antitumorigenic activity. J Biol Chem 2003; 278: 5845-53.
249. Baek SJ, Kim JS, Nixon JB, DiAugustine RP, Eling TE. Expression of NAG-1, a transforming growth factor-beta superfamily member, by troglitazone requires the early growth response gene EGR-1. J Biol Chem 2004; 279: 6883-92.
250. Yamaguchi K, Lee SH, Eling TE, Baek SJ. Identification of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) as a novel downstream target of phosphatidylinositol 3-kinase/AKT/GSK-3beta pathway. J Biol Chem 2004; 279: 49617-23.
251. Eling TE, Baek SJ, Shim M, Lee CH. NSAID activated gene (NAG-1), a modulator of tumorigenesis. J Biochem Mol Biol 2006; 39: 649-55.
252. Baek SJ, Wilson LC, Eling TE. Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53. Carcinogenesis 2002; 23: 425-34.
253. Bottone FG Jr, Baek SJ, Nixon JB, Eling TE. Diallyl disulfide (DADS) induces the antitumorigenic NSAID-activated gene (NAG-1) by a p53-dependent mechanism in human colorectal HCT 116 cells. J Nutr 2002; 132: 773-8.
254. Wilson LC, Baek SJ, Call A, Eling TE. Nonsteroidal antiinflammatory drug-activated gene (NAG-1) is induced by genistein through the expression of p53 in colorectal cancer cells. Int J Cancer 2003; 105: 747-53.
255. Baek SJ, Kim J, Jackson FR, Eling TE, McEntee MF, Lee S. Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells. Carcinogenesis 2004; 25: 2425-32.
256. Devchand PR, Ijpenberg A, Devesvergne B, Wahli W. PPARs: nuclear receptors for fatty acids, eicosanoids, and xenobiotics. Adv Exp Med Biol 1999; 469: 231-6.
257. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20: 649-88.
258. Kubuta T, Koshizuka K and Williamson EA. Ligand for Peroxisome proliferator-activated receptor has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res 1998; 58: 3344-52.
259. Li MY, Deng H, Zhao JM, Dai D, Tan XY. PPARg pathway activation results in apoptosis and COX-2 inhibition in HepG2 cells. World J Gastroenterol 2003; 9: 1220-6.
260. Cory S, Adams JM. The Bcl2 family: regulators of the cellular lifeor-death switch. Nat Rev Cancer 2002; 2: 647-56.
261. Takahashi N, Okumaura T, Motomura W. Activation of PPARgamma inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett 1999; 455: 135-9.
262. Yang LW, Frucht H. Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Carcinogenesis 2001; 22: 1379-83.
263. Gregorieff A, Clevers H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev 2005; 19(8): 877-90.
264. Staal FJ, Luis TC, Tiemessen MM. WNT signalling in the immune system: WNT is spreading its wings. Nat Rev Immunol 2008; 8: 581-93.
265. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759-67.
266. Nishisho I, Nakamura Y, Miyoshi Y, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991; 253: 665-9.
267. Gumbiner BM. Regulation of cadherin adhesive activity. J Cell Biol 2000; 148(3): 399-403.
268. Bradley RS, Cowin P, Brown A.M. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion. J Cell Biol 1993; 123(6 Pt 2): 1857-65.
269. Hinck L, Nelson WJ, Papkoff J. Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin. J Cell Biol 1994; 124(5): 729-41.
270. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991; 251(5000): 1451-5.
271. Roccaro AM, Leleu X, Sacco A, et al. Resveratrol exertsantiproliferative activity and induces apoptosis in Waldenstrom's macroglobulinemia. Clin Cancer Res 2008; 14: 1849-58.
272. Vanamala J, Reddivari L, Radhakrishnan S, Tarver C. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways. BMC Cancer 2010; 10: 238.
273. Shan BE, Wang MX, Li RQ. Quercetin inhibits human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/beta-catenin signaling pathway. Cancer Invest 2009; 27(6): 604-12.
274. Bhat TA, Singh RP. Tumor angiogenesis-a potential target in cancer chemoprevention. Food Chem Toxicol 2008; 46(4): 1334-45.
275. Zebrowski BK, Wilson MR, Bucana CD, McConkey DJ, McMahon G, Ellis LM. Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res 1999; 59: 5412-6.
276. Emile EV, Patricia AD. Tumor angiogenesis and microcirculation. New York, Basel: Marcel Dekker Inc. (2001)
277. Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophy Res Comm 1992; 189(2): 824-31.
278. Kazemi S, Wenzel D, Kolossov E, et al. Differential role of bFGF and VEGF for vasculogenesis. Cell Physiol Biochem 2002; 12: 55-62.
279. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991; 64(2): 327-36.
280. Matrisian LM. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 1990; 6(4): 121-5.
281. Bancroft CC, Chen Z, Yeh J. Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF-kappaB and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines. Int J Cancer 2002; 99(4): 538-48.
282. Ogawa S, Yoshida S, Ono M, et al. Induction of macrophage inflammatory protein-1 alpha and vascular endothelial growth factor during inflammatory neovascularization in the mouse cornea. Angiogenesis 1999; 3(4): 327-34.
283. Bhat TA, Singh RP. Tumor angiogenesis-A potential target in cancer chemoprevention. Food Chem Toxicol 2008; 46: 1334-45.
284. Vayalil PK, Mittal A, Katiyar SK. Proanthocyanidins from grape seeds inhibit expression of matrix metalloproteinases in human prostate carcinoma cells, which is associated with the inhibition of activation of MAPK and NF kappa B. Carcinogenesis 2004; 25(6): 987-95.
285. Kousidou OC, Mitropoulou TN, Roussidis AE, et al. Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors. Int J Oncol 2005; 26(4): 1101-9.
286. Surh Y, Kundu JK. Cancer preventive phytochemicals as speed breakers in inflammatory signaling involved in aberrant COX-2 expression. Curr Cancer Drug Targets 2007; 7: 447-58.
287. Höckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001; 93(4): 266-76.
288. Humar R, Kiefer FN, Berns H, Resink TJ, Battegay E.J. Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signaling. FASEB J 2002; 16: 771-80.
289. Krishnamachary B, Berg-Dixon S, Kelly B, et al. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor. Cancer Res 2003; 63: 1138-43.
290. 2 tension. Proc Natl Acad Sci USA 1995; 92: 5510-4.
291. Brugarolas J, Kaelin WG Jr. Dysregulation of HIF and VEGF is an unifying feature of the familial hamartoma syndromes. Cancer cell 2004; 6: 7-10.
292. Ravi R, Mookerjee B, Bhujwalla ZM, et al. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α. Genes Dev 2000; 14: 34-44.
293. Land SC, Tee AR. Hypoxia-inducible factor 1α is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. J Biol Chem 2007; 282: 20534-43.
294. Kizaka-Kondoh S, Inoue M, Harada H, Hiraoka M. Tumor hypoxia: A target for selective cancer therapy. Cancer Sci 2003; 94(12): 1021-8.
295. Ko JK, Lee SS, Martin H. Phytochemicals as modulators of PPARs and RXRs. PPAR Res 2010; 2010: 407650. (Editorial)