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研究生:郭啟利
研究生(外文):Chi-Li Kuo
論文名稱:小蘗鹼抑制COX-2表現及誘發口腔癌細胞進行凋亡之機轉研究
論文名稱(外文):Berberine Inhibits COX-2 Expression and Induces Apoptosis in Oral Cancer Cells
指導教授:劉宗榮劉宗榮引用關係
指導教授(外文):Tsung-Yun Liu
學位類別:博士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:150
中文關鍵詞:小蘗鹼環氧化酶前列腺素發炎反應細胞凋亡
外文關鍵詞:Berberinecyclooxygenaseprostaglandininflammationapoptosis
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小蘗鹼具有抗發炎反應的作用,但是作用機轉尚未清楚。本實驗藉由觀察小蘗鹼對於發炎反應中的前列腺素生成的關鍵酵素 cyclooxygenase-2 (COX-2) 蛋白的影響,進而了解小蘗鹼的抗發炎作用機轉以及對癌細胞所造成的影響。OC2 及 KB 兩株口腔癌細胞,不論是否受到 10 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) 的作用,經過 12 小時不同濃度的小蘗鹼處理均能減少 COX-2 下游 PGE2 的生成。進一步分析發現,在小蘗鹼 3 小時作用下,僅抑制COX-2 而非 COX-1 蛋白的表現,但不影響 COX-1 及 COX-2 蛋白的酵素活性。藉由凝膠電泳遷移分析法 (electrophoretic mobility shift assay, EMSA),得知口腔癌細胞在小蘗鹼 2 小時作用下,細胞中 activator protein 1 (AP-1) 蛋白與其對應的寡核苷序列之結合受到直接的抑制。以鹿角菜膠 (carrageenan) 注射在 Wistar 老鼠背部形成的空腔進行發炎反應實驗,發現小蘗鹼減低了空腔中組織液的滲出與滲出液中的 PGE2 的含量,顯示小蘗鹼具有抗發炎效果。
小蘗鹼降低 COX-2 蛋白的表現也抑制了口腔癌細胞生長。KB 細胞經過 12 小時小蘗鹼的作用,細胞生長受到了抑制;PGE2 的加入可以部份逆轉小蘗鹼對於細胞生長的抑制作用。3 或 6 個小時小蘗鹼的作用,可使 KB 細胞中抗凋亡蛋白 MCL-1 的表現量降低,而另一個抗凋亡蛋白 BCL-2 的表現量則不受小蘗鹼影響。進一步分析發現,小蘗鹼對於 MCL-1 蛋白表現的影響,部份的原因可能是:小蘗鹼降低 COX-2 蛋白表現,導致 PGE2 生成受到抑制,而減少了 AKT 蛋白的磷酸化,阻斷了經過 PI3K/AKT 路徑的訊號傳遞而使得 MCL-1 抗凋亡蛋白的表現降低。
Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation, yet the exact mechanism is unknown. Because cyclooxygenase-2 (COX-2) plays a key role in prostaglandins (PGs) synthesis which is elevated in inflammation, this thesis examined whether the anti-inflammatory mechanism of berberine is mediated through COX-2 regulation. In oral cancer cell line OC2 and KB cells, a 12 hr berberine treatment (1, 10, and 100 μM) reduced prostaglandin E2 (PGE2) production dose-dependently with or without 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 nM) induction. This berberine induced effect occurred rapidly in 3 hr treatment as a result of reduced COX-2 protein, but not enzyme activity. The electrophoretic mobility shift assay (EMSA) revealed that activator protein 1 (AP-1) binding was decreased in oral cancer cells treated with berberine for 2 hr. Further analysis showed that berberine inhibited AP-1 binding directly. These anti-inflammatory effects paralleled to the in vivo results where berberine pretreatment of Wistar rat inhibited the production of exudates and PGE2 in carrageenan induced air pouch.
Biochemical influence of berberine-induced COX-2 reduction and apoptosis was also explored. Berberine induced apoptosis in KB cells after 12 hr treatment, and was partially reversed by incorporation of PGE2. A three hour and 6 hr berberine treatment inhibited COX-2 and MCL-1 expression dose-dependently but not BCL-2. PGE2 induced COX-2 and MCL-1 expression and reversed the repressive effect of berberine on MCL-1. In addition, PGE2 treatment had no effect on the total level of AKT, but slightly reversed the phosphorylated AKT, which were decreased by berberine. These results suggest that berberine-induced apoptosis might be COX-2 dependent and are related to decreased AKT phosphorylation and MCL-1 expression.
1 Ikram M: A review on the chemical and pharmacological aspects of genus Berberis. Planta Med 28: 353-358, 1975.
2 張志玲: 古物中尋找科學靈感. 科學發展 375: 63-67, 2004.
3 Gibbs PJ and Seddon KR: Berberine and Huangbo: Ancient Colorants and Dyes. Vol 2. London, British Library, 1998
4 中華藥典. 行政院衛生署中華藥典編修委員會, 3 edition, 1980
5 Greenaway AJ, Thorpe JF and Robinson R: The Life and Work of Professor William Henry Perkin. RoyalChemical Society, 1932
6 Kametani T, Noguchi I, Saito K and Kaneda S: Studies on the syntheses of heterocyclic compounds. CCCII. Alternative total syntheses of (+ -)-nandinine, (+ -)-canadine, and berberine iodide. J Chem Soc [Perkin 1] 15: 2036-2038, 1969.
7 吳佳錩: 生藥學輯要. 偉成出版社, 1979
8 Baird AW, Taylor CT and Brayden DJ: Non-antibiotic anti-diarrhoeal drugs: factors affecting oral bioavailability of berberine and loperamide in intestinal tissue. Adv Drug Deliv Rev 23: 111-120, 1997.
9 Brewster M and Bodor N: Improved delivery through biological membranes XVI. Enhancement of the brain-specificity of a dihydropyridine formed from pyridinium salt drug delivery system by controlled infusion. J Parenter Sci Technol 37: 159-164, 1983.
10 Tsai P and Tsai TH: Simultaneous determination of berberine in rat blood, liver and bile using microdialysis coupled to high-performance liquid chromatography. J Chromatogr A 961: 125-130, 2002.
11 Bhide MB, Chavan SR and Dutta NK: Absorption, distribution and excretion of berberine. Indian J Med Res 57: 2128-2131, 1969.
12 Sabir M, Akhter MH and Bhide NK: Further studies on pharmacology of berberine. Indian J Physiol Pharmacol 22: 9-2, 1978.
13 Lin N, Gao X, Li J and Zhu J: Influence of huanglian and berberine on the erythrocytic osmotic fragilitas of experimental glucose-6-phosphate dehydrogenase deficiency in rats. Zhongguo Zhong Yao Za Zhi 23: 562-564, back cover, 1998.
14 Ho NK: Traditional Chinese medicine and treatment of neonatal jaundice. Singapore Med J 37: 645-651, 1996.
15 Kulkarni SK, Dandiya PC and Varandani NL: Pharmacological investigations of berberine sulphate. Jpn J Pharmacol 22: 11-16, 1972.
16 Muller K, Ziereis K and Gawlik I: The antipsoriatic Mahonia aquifolium and its active constituents; II. Antiproliferative activity against cell growth of human keratinocytes. Planta Med 61: 74-75, 1995.
17 Khin Maung U, Myo K, Nyunt Nyunt W, Aye K and Tin U: Clinical trial of berberine in acute watery diarrhoea. Br Med J (Clin Res Ed) 291: 1601-1605, 1985.
18 Choudhry VP, Sabir M and Bhide VN: Berberine in giardiasis. Indian Pediatr 9: 143-146, 1972.
19 Vennerstrom JL, Lovelace JK, Waits VB, Hanson WL and Klayman DL: Berberine derivatives as antileishmanial drugs. Antimicrob Agents Chemother 34: 918-921, 1990.
20 Vennerstrom JL and Klayman DL: Protoberberine alkaloids as antimalarials. J Med Chem 31: 1084-1087, 1988.
21 Marin-Neto JA, Maciel BC, Secches AL and Gallo Junior L: Cardiovascular effects of berberine in patients with severe congestive heart failure. Clin Cardiol 11: 253-260, 1988.
22 Creasey WA: Plant Alkaloids. In Cancer, a Comprehensive Treatise: Chemotherapy. FF Becker. Vol 5. New York and London, Plenum Press, 1977, pp 379-425
23 Borodina VM, Kirianova EE, Fedorova OV and Zelenin AV: Cytochemical properties of interphase chromatin condensed as a result of treatment with caffeine. Exp Cell Res 122: 391-394, 1979.
24 Ridler PJ and Jennings BR: Electro-optical fluorescence studies on the DNA binding of medically active drugs. Phys Med Biol 28: 625-632, 1983.
25 Mikes V and Dadak V: Berberine derivatives as cationic fluorescent probes for the investigation of the energized state of mitochondria. Biochim Biophys Acta 723: 231-239, 1983.
26 Palmery M, Leone MG, Pimpinella G and Romanelli L: Effects of Hydrastis Canadensis L. and the Two Major Alkaloids Berberire and Hydrastine on Rabbit Aorta. Pharmacol Res 27 Suppl 1: 73-74, 1993.
27 Luo LY, Cheng B, Fang DC and Jiang MX: Alpha-adrenoceptor blocking effect of berberine in isolated rat anococcygeus muscles and rabbit aorta strips. Zhongguo Yao Li Xue Bao 7: 407-409, 1986.
28 Wang YX, Zheng YM and Zhou XB: Inhibitory effects of berberine on ATP-sensitive K+ channels in cardiac myocytes. Eur J Pharmacol 316: 307-315, 1996.
29 Huang CG, Chu ZL and Yang ZM: Effects of berberine on synthesis of platelet TXA2 and plasma PGI2 in rabbits. Zhongguo Yao Li Xue Bao 12: 526-528, 1991.
30 Creasey WA: Biochemical effects of berberine. Biochem Pharmacol 28: 1081-1084, 1979.
31 Nishino H, Kitagawa K, Fujiki H and Iwashima A: Berberine sulfate inhibits tumor-promoting activity of teleocidin in two-stage carcinogenesis on mouse skin. Oncology 43: 131-134, 1986.
32 Zhang RX, Dougherty DV and 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) 103: 658-665, 1990.
33 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 90: 10-14, 1991.
34 Chi CW, Chang YF, Chao TW, Chiang SH, P''Eng F K, Lui WY and Liu TY: Flowcytometric analysis of the effect of berberine on the expression of glucocorticoid receptors in human hepatoma HepG2 cells. Life Sci 54: 2099-2107, 1994.
35 Chen KT, Hao DM, Liu ZX, Chen YC and You ZS: Effect of berberine alone or in combination with argon ion laser treatment on 9L rat glioma cell line. Chin Med J (Engl) 107: 808-812, 1994.
36 Lee SJ, Kim JB, Lee SW and Kim JH: Enhanced cytotoxicity of berberine and some anticancer nucleotides against tumor cell lines. Arch Pharm Res 18: 138-139, 1995.
37 Kuo CL, Chou CC and Yung BY: Berberine complexes with DNA in the berberine-induced apoptosis in human leukemic HL-60 cells. Cancer Lett 93: 193-200, 1995.
38 Yang IW, Chou CC and Yung BY: Dose-dependent effects of berberine on cell cycle pause and apoptosis in BALB/c 3T3 cells. Naunyn Schmiedebergs Arch Pharmacol 354: 102-108, 1996.
39 Valeriote F, Corbett T, Edelstein M and Baker L: New in vitro screening model for the discovery of antileukemic anticancer agents. Cancer Invest 14: 124-141, 1996.
40 Fukuda K, Hibiya Y, Mutoh M, Koshiji M, Akao S and Fujiwara H: Inhibition of activator protein 1 activity by berberine in human hepatoma cells. Planta Med 65: 381-383, 1999.
41 Fukuda K, Hibiya Y, Mutoh M, Koshiji M, Akao S and Fujiwara H: Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol 66: 227-233, 1999.
42 Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature - New Biology 231: 232-235, 1971.
43 Fu JY, Masferrer JL, Seibert K, Raz A and Needleman P: The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem 265: 16737-16740, 1990.
44 Masferrer JL, Zweifel BS, Seibert K and Needleman P: Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest 86: 1375-1379, 1990.
45 Xie WL, Chipman JG, Robertson DL, Erikson RL and Simmons DL: Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A 88: 2692-2696, 1991.
46 Loll PJ, Picot D and Garavito RM: The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nat Struct Biol 2: 637-643, 1995.
47 Smith WL and DeWitt DL: Biochemistry of prostaglandin endoperoxide H synthase-1 and synthase-2 and their differential susceptibility to nonsteroidal anti-inflammatory drugs. Semin Nephrol 15: 179-194, 1995.
48 Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E and Tanabe T: Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Eur J Biochem 221: 889-897, 1994.
49 Marnett LJ, Rowlinson SW, Goodwin DC, Kalgutkar AS and Lanzo CA: Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition. J Biol Chem 274: 22903-22906, 1999.
50 Hawkey CJ: COX-2 inhibitors. Lancet 353: 307-314, 1999.
51 O''Banion MK, Winn VD and Young DA: cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc Natl Acad Sci U S A 89: 4888-4892, 1992.
52 Williams CS and DuBois RN: Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 270: G393-400, 1996.
53 Morita I, Schindler M, Regier MK, Otto JC, Hori T, DeWitt DL and Smith WL: Different intracellular locations for prostaglandin endoperoxide H synthase-1 and -2. J Biol Chem 270: 10902-10908, 1995.
54 O''Neill GP and Ford-Hutchinson AW: Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 330: 156-160, 1993.
55 Vane JR and Botting RM: Selective COX-2 inhibitors. 1st edition. Berlin, William Harvey Press, 1997
56 Shaw G and Kamen R: A conserved AU sequence from the 3'' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46: 659-667, 1986.
57 Cok SJ and Morrison AR: The 3''-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency. J Biol Chem 276: 23179-23185, 2001.
58 Newton R, Seybold J, Liu SF and Barnes PJ: Alternate COX-2 transcripts are differentially regulated: implications for post-transcriptional control. Biochem Biophys Res Commun 234: 85-89, 1997.
59 Picot D, Loll PJ and Garavito RM: The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature 367: 243-249, 1994.
60 Nemeth JF, Hochgesang GP, Jr., Marnett LJ, Caprioli RM and Hochensang GP, Jr.: Characterization of the glycosylation sites in cyclooxygenase-2 using mass spectrometry. Biochemistry 40: 3109-3116, 2001.
61 Kargman S, Charleson S, Cartwright M, Frank J, Riendeau D, Mancini J, Evans J and O''Neill G: Characterization of Prostaglandin G/H Synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts. Gastroenterology 111: 445-454, 1996.
62 Smith CJ, Zhang Y, Koboldt CM, Muhammad J, Zweifel BS, Shaffer A, Talley JJ, Masferrer JL, Seibert K and Isakson PC: Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci U S A 95: 13313-13318, 1998.
63 Mizuno H, Sakamoto C, Matsuda K, Wada K, Uchida T, Noguchi H, Akamatsu T and Kasuga M: Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology 112: 387-397, 1997.
64 Kawai S: Cyclooxygenase selectivity and the risk of gastro-intestinal complications of various non-steroidal anti-inflammatory drugs: a clinical consideration. Inflamm Res 47 Suppl 2: S102-106, 1998.
65 Kaufmann WE, Andreasson KI, Isakson PC and Worley PF: Cyclooxygenases and the central nervous system. Prostaglandins 54: 601-624, 1997.
66 Taniguchi Y, Yokoyama K, Inui K, Deguchi Y, Furukawa K and Noda K: Inhibition of brain cyclooxygenase-2 activity and the antipyretic action of nimesulide. Eur J Pharmacol 330: 221-229, 1997.
67 Willingale HL, Gardiner NJ, McLymont N, Giblett S and Grubb BD: Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 122: 1593-1604, 1997.
68 Khan KN, Venturini CM, Bunch RT, Brassard JA, Koki AT, Morris DL, Trump BF, Maziasz TJ and Alden CL: Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity. Toxicol Pathol 26: 612-620, 1998.
69 Khan KN, Paulson SK, Verburg KM, Lefkowith JB and Maziasz TJ: Pharmacology of cyclooxygenase-2 inhibition in the kidney. Kidney Int 61: 1210-1219, 2002.
70 FitzGerald GA, Cheng Y and Austin S: COX-2 inhibitors and the cardiovascular system. Clin Exp Rheumatol 19: S31-36, 2001.
71 Kay-Mugford PA, Benn SJ, LaMarre J and Conlon PD: Cyclooxygenase expression in canine platelets and Madin-Darby canine kidney cells. Am J Vet Res 61: 1512-1516, 2000.
72 Hennan JK, Huang J, Barrett TD, Driscoll EM, Willens DE, Park AM, Crofford LJ and Lucchesi BR: Effects of selective cyclooxygenase-2 inhibition on vascular responses and thrombosis in canine coronary arteries. Circulation 104: 820-825, 2001.
73 Kopp E and Ghosh S: Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 265: 956-959, 1994.
74 Howe LR, Crawford HC, Subbaramaiah K, Hassell JA, Dannenberg AJ and Brown AM: PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 276: 20108-20115, 2001.
75 Fosslien E: Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 30: 3-21, 2000.
76 Sheng H, Shao J, Dixon DA, Williams CS, Prescott SM, DuBois RN and Beauchamp RD: Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA. J Biol Chem 275: 6628-6635, 2000.
77 Turini ME and DuBois RN: Cyclooxygenase-2: a therapeutic target. Annu Rev Med 53: 35-57, 2002.
78 Smith WL, DeWitt DL and Garavito RM: Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69: 145-182, 2000.
79 Subbaramaiah K, Norton L, Gerald W and Dannenberg AJ: Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem 277: 18649-18657, 2002.
80 Zhang F, Altorki NK, Mestre JR, Subbaramaiah K and Dannenberg AJ: Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis. 20: 445-451, 1999.
81 Subbaramaiah K, Cole PA and Dannenberg AJ: Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein/p300-dependent and -independent mechanisms. Cancer Res 62: 2522-2530, 2002.
82 Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A and Dannenberg AJ: Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem 274: 10911-10915, 1999.
83 Callejas NA, Castrillo A, Bosca L and Martin-Sanz P: Inhibition of prostaglandin synthesis up-regulates cyclooxygenase-2 induced by lipopolysaccharide and peroxisomal proliferators. J Pharmacol Exp Ther 288: 1235-1241, 1999.
84 Inoue H, Tanabe T and Umesono K: Feedback control of cyclooxygenase-2 expression through PPARgamma. J Biol Chem 275: 28028-28032, 2000.
85 Meade EA, McIntyre TM, Zimmerman GA and Prescott SM: Peroxisome proliferators enhance cyclooxygenase-2 expression in epithelial cells. J Biol Chem 274: 8328-8334, 1999.
86 Chinery R, Coffey RJ, Graves-Deal R, Kirkland SC, Sanchez SC, Zackert WE, Oates JA and Morrow JD: Prostaglandin J2 and 15-deoxy-delta12,14-prostaglandin J2 induce proliferation of cyclooxygenase-depleted colorectal cancer cells. Cancer Res 59: 2739-2746, 1999.
87 Dixon DA, Kaplan CD, McIntyre TM, Zimmerman GA and Prescott SM: Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3''-untranslated region. J Biol Chem 275: 11750-11757, 2000.
88 Shao J, Sheng H, Inoue H, Morrow JD and DuBois RN: Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem 275: 33951-33956, 2000.
89 Zhang Z, Sheng H, Shao J, Beauchamp RD and DuBois RN: Posttranscriptional regulation of cyclooxygenase-2 in rat intestinal epithelial cells. Neoplasia 2: 523-530, 2000.
90 Dixon DA, Tolley ND, King PH, Nabors LB, McIntyre TM, Zimmerman GA and Prescott SM: Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest 108: 1657-1665, 2001.
91 Lasa M, Mahtani KR, Finch A, Brewer G, Saklatvala J and Clark AR: Regulation of cyclooxygenase 2 mRNA stability by the mitogen-activated protein kinase p38 signaling cascade. Mol Cell Biol 20: 4265-4274, 2000.
92 Marnett LJ, Reed GA and Dennison DJ: Prostaglandin synthetase dependent activation of 7,8-dihydro-7,8-dihydroxy-geno (a) pyrene to mutagenic derivativies. Biochem Biophys Res Commun 82: 210-216, 1978.
93 Eling TE and Curtis JF: Xenobiotic metabolism by prostaglandin H synthase. Pharmacol Ther 53: 261-273, 1992.
94 Janot F, Massaad L, Ribrag V, de Waziers I, Beaune PH, Luboinski B, Parise O, Jr., Gouyette A and Chabot GG: Principal xenobiotic-metabolizing enzyme systems in human head and neck squamous cell carcinoma. Carcinogenesis 14: 1279-1283, 1993.
95 Wiese FW, Thompson PA and Kadlubar FF: Carcinogen substrate specificity of human COX-1 and COX-2. Carcinogenesis 22: 5-10, 2001.
96 Kim PM, DeBoni U and Wells PG: Peroxidase-dependent bioactivation and oxidation of DNA and protein in benzo[a]pyrene-initiated micronucleus formation. Free Radic Biol Med 23: 579-596, 1997.
97 Morel Y, Mermod N and Barouki R: An autoregulatory loop controlling CYP1A1 gene expression: role of H(2)O(2) and NFI. Mol Cell Biol 19: 6825-6832, 1999.
98 Kelley DJ, Mestre JR, Subbaramaiah K, Sacks PG, Schantz SP, Tanabe T, Inoue H, Ramonetti JT and Dannenberg AJ: Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells. Carcinogenesis 18: 795-799, 1997.
99 Dannenberg AJ and Zakim D: Chemoprevention of colorectal cancer through inhibition of cyclooxygenase-2. Semin Oncol 26: 499-504, 1999.
100 Watson AJ: Chemopreventive effects of NSAIDs against colorectal cancer: regulation of apoptosis and mitosis by COX-1 and COX-2. Histol Histopathol 13: 591-597, 1998.
101 Tsujii M and DuBois RN: Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83: 493-501, 1995.
102 Sheng H, Shao J, Morrow JD, Beauchamp RD and DuBois RN: Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58: 362-366, 1998.
103 Liu CH, Chang S-H, Narko K, Trifan OC, Wu M-T, Smith E, Haudenschild C, Lane TF and Hla T: Overexpression of Cyclooxygenase-2 Is Sufficient to Induce Tumorigenesis in Transgenic Mice. J Biol Chem 276: 18563-18569, 2001.
104 Cao Y and Prescott SM: Many actions of cyclooxygenase-2 in cellular dynamics and in cancer. J Cell Physiol 190: 279-286, 2002.
105 Sawaoka H, Kawano S, Tsuji S, Tsujii M, Gunawan ES, Takei Y, Nagano K and Hori M: Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice. Am J Physiol 274: G1061-1067, 1998.
106 Nishimura G, Yanoma S, Mizuno H, Kawakami K and Tsukuda M: A selective cyclooxygenase-2 inhibitor suppresses tumor growth in nude mouse xenografted with human head and neck squamous carcinoma cells. Jpn J Cancer 90: 1152-1162, 1999.
107 Liu XH, Yao S, Kirschenbaum A and Levine AC: NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells. Cancer Res 58: 4245-4249, 1998.
108 Hara A, Yoshimi N, Niwa M, Ino N and Mori H: Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines. Jpn J Cancer Res 88: 600-604, 1997.
109 Li M, Lotan R, Levin B, Tahara E, Lippman SM and Xu XC: Aspirin induction of apoptosis in esophageal cancer: a potential for chemoprevention. Cancer Epidemiol Biomarkers Prev 9: 545-549, 2000.
110 Nzeako UC, Guicciardi ME, Yoon JH, Bronk SF and Gores GJ: COX-2 inhibits Fas-mediated apoptosis in cholangiocarcinoma cells. Hepatology 35: 552-559, 2002.
111 Lin MT, Lee RC, Yang PC, Ho FM and Kuo ML: Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem 276: 48997-49002, 2001.
112 Zhang Z and DuBois RN: Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. Gastroenterology 118: 1012-1017, 2000.
113 Camandola S and Mattson MP: Pro-apoptotic action of PAR-4 involves inhibition of NF-kappaB activity and suppression of BCL-2 expression. J Neurosci Res 61: 134-139, 2000.
114 McGinty A, Chang YW, Sorokin A, Bokemeyer D and Dunn MJ: Cyclooxygenase-2 expression inhibits trophic withdrawal apoptosis in nerve growth factor-differentiated PC12 cells. J Biol Chem 275: 12095-12101, 2000.
115 Weitzman SA and Gordon LI: Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. Blood 76: 655-663, 1990.
116 Baker PE, Fahey JV and Munck A: Prostaglandin inhibition of T-cell proliferation is mediated at two levels. Cell Immunol 61: 52-61, 1981.
117 Brunda MJ, Herberman RB and Holden HT: Inhibition of murine natural killer cell activity by prostaglandins. J Immunol 124: 2682-2687, 1980.
118 Goodwin JS, Bankhurst AD and Messner RP: Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell. J Exp Med 146: 1719-1734, 1977.
119 Goodwin JS and Ceuppens J: Regulation of the immune response by prostaglandins. J Clin Immunol 3: 295-315, 1983.
120 Taffet SM and Russell SW: Macrophage-mediated tumor cell killing: regulation of expression of cytolytic activity by prostaglandin E. J Immunol 126: 424-427, 1981.
121 Kunkel SL, Wiggins RC, Chensue SW and Larrick J: Regulation of macrophage tumor necrosis factor production by prostaglandin E2. Biochem Biophys Res Commun 137: 404-410, 1986.
122 Kambayashi T, Alexander HR, Fong M and Strassmann G: Potential involvement of IL-10 in suppressing tumor-associated macrophages. Colon-26-derived prostaglandin E2 inhibits TNF-alpha release via a mechanism involving IL-10. J Immunol 154: 3383-3390, 1995.
123 Grinwich KD and Plescia OJ: Tumor-mediated immunosuppression: prevention by inhibitors of prostaglandin synthesis. Prostaglandins 14: 1175-1182, 1977.
124 Han T and Takita H: Indomethacin-mediated enhancement of lymphocyte response to mitogens in healthy subjects and lung cancer patients. Cancer 46: 2416-2420, 1980.
125 Tilden AB and Balch CM: Indomethacin enhancement of immunocompetence in melanoma patients. Surgery 90: 77-84, 1981.
126 Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82: 4-6, 1990.
127 Marme D: Tumor angiogenesis: the pivotal role of vascular endothelial growth factor. World J Urol 14: 166-174, 1996.
128 Chiarugi V, Magnelli L and Gallo O: Cox-2, iNOS and p53 as play-makers of tumor angiogenesis. Bioorg Med Chem Lett 2: 715-719, 1998.
129 Gallo O, Franchi A, Magnelli L, Sardi I, Vannacci A, Boddi V, Chiarugi V and Masini E: Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis. Neoplasia 3: 53-61, 2001.
130 Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M and DuBois RN: Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93: 705-716, 1998.
131 Williams CS, Tsujii M, Reese J, Dey SK and DuBois RN: Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 105: 1589-1594, 2000.
132 Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ and Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60: 1306-1311, 2000.
133 Tsujii M, Kawano S and DuBois RN: COX-2 expression in human colon cancer cells increases metastatic potential. Proc. Natl Acad Sci USA 94: 3336-3340, 1997.
134 Attiga FA, Fernandez PM, Weeraratna AT, Manyak MJ and Patierno SR: Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell invasiveness and reduce the release of matrix metalloproteinases. Cancer Res 60: 4629-4637, 2000.
135 Dohadwala M, Luo J, Zhu L, Lin Y, Dougherty GJ, Sharma S, Huang M, Pold M, Batra RK and Dubinett SM: Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44. J Biol Chem 276: 20809-20812, 2001.
136 Tomozawa S, Nagawa H, Tsuno N, Hatano K, Osada T, Kitayama J, Sunami E, Nita ME, Ishihara S, Yano H, Tsuruo T, Shibata Y and Muto T: Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522. Br J Cancer 81: 1274-1279, 1999.
137 Patel VA, Dunn MJ and Sorokin A: Regulation of MDR-1 (P-glycoprotein) by cyclooxygenase-2. J Biol Chem 277: 38915-38920, 2002.
138 Wong DY, Chang KW, Chen CF and Chang RC: Characterization of two new cell lines derived from oral cavity human squamous cell carcinomas--OC1 and OC2. J Oral Maxillofac Surg 48: 385-390, 1990.
139 Yasukawa K, Takido M, Ikekawa T, Shimada F, Takeuchi M and Nakagawa S: Relative inhibitory activity of berberine-type alkaloids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Chem Pharm Bull (Tokyo) 39: 1462-1465, 1991.
140 Ivanovska N and Philipov S: Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions and pure alkaloids. Int J Immunopharmacol 18: 553-561, 1996.
141 Yesilada E and Kupeli E: Berberis crataegina DC. root exhibits potent anti-inflammatory, analgesic and febrifuge effects in mice and rats. J Ethnopharmacol 79: 237-248, 2002.
142 New P: Cyclooxygenase in the treatment of glioma: its complex role in signal transduction. Cancer Control 11: 152-164, 2004.
143 Ikekawa T and Ikeda Y: Antitumor activity of 13-methyl-berberrubine derivatives. J Pharmacobiodyn 5: 469-474, 1982.
144 Liang YC, Huang YT, Tsai SH, Lin-Shiau SY, Chen CF and Lin JK: Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis 20: 1945-1952, 1999.
145 Goel A, Boland CR and Chauhan DP: Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells. Cancer Lett 172: 111-118, 2001.
146 Pilch DS, Yu C, Makhey D, LaVoie EJ, Srinivasan AR, Olson WK, Sauers RR, Breslauer KJ, Geacintov NE and Liu LF: Minor groove-directed and intercalative ligand-DNA interactions in the poisoning of human DNA topoisomerase I by protoberberine analogs. Biochemistry 36: 12542-12553, 1997.
147 Schmeller T, Latz-Bruning B and Wink M: Biochemical activities of berberine, palmatine and sanguinarine mediating chemical defence against microorganisms and herbivores. Phytochemistry 44: 257-266, 1997.
148 Mazzini S, Bellucci MC and Mondelli R: Mode of binding of the cytotoxic alkaloid berberine with the double helix oligonucleotide d(AAGAATTCTT)(2). Bioorg Med Chem 11: 505-514, 2003.
149 Krishnan P and Bastow KF: The 9-position in berberine analogs is an important determinant of DNA topoisomerase II inhibition. Anticancer Drug Des 15: 255-264, 2000.
150 Kobayashi Y, Yamashita Y, Fujii N, Takaboshi K, Kawakami T, Kawamura M, Mizukami T and Nakano H: Inhibitors of DNA topoisomerase I and II isolated from the Coptis rhizomes. Planta Med 61: 414-418, 1995.
151 Venkat K, Brown MD and Barkin R: Nonsteroidal anti-inflammatory drugs and gastroduodenal injury. Am J Ther 5: 263-272, 1998.
152 Raskin JB: Gastrointestinal effects of nonsteroidal anti-inflammatory therapy. Am J Med 106: 3S-12S, 1999.
153 Epstein M: Non-steroidal anti-inflammatory drugs and the continuum of renal dysfunction. J Hypertens 20 Suppl 6: S17-23, 2002.
154 Ray WA, MacDonald TM, Solomon DH, Graham DJ and Avorn J: COX-2 selective non-steroidal anti-inflammatory drugs and cardiovascular disease. Pharmacoepidemiol Drug Saf 12: 67-70, 2003.
155 D''Acquisto F, Ialenti A, Ianaro A, Di Vaio R and Carnuccio R: Local administration of transcription factor decoy oligonucleotides to nuclear factor-kappaB prevents carrageenin-induced inflammation in rat hind paw. Gene Ther 7: 1731-1737, 2000.
156 Nishida S, Kikuichi S, Yoshioka S, Tsubaki M, Fujii Y, Matsuda H, Kubo M and Irimajiri K: Induction of apoptosis in HL-60 cells treated with medicinal herbs. Am J Chin Med 31: 551-562, 2003.
157 Hida T, Leyton J, Makheja AN, Ben-Av P, Hla T, Martinez A, Mulshine J, Malkani S, Chung P and Moody TW: Non-small cell lung cancer cycloxygenase activity and proliferation are inhibited by non-steroidal antiinflammatory drugs. Anticancer Res 18: 775-782, 1998.
158 Sheng H, Shao J, Washington MK and DuBois RN: Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 276: 18075-18081, 2001.
159 Lin HL, Liu TY, Wu CW and Chi CW: Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel. Br J Cancer 81: 416-422, 1999.
160 Kim SA, Kwon Y, Kim JH, Muller MT and Chung IK: Induction of topoisomerase II-mediated DNA cleavage by a protoberberine alkaloid, berberrubine. Biochemistry 37: 16316-16324, 1998.
161 Mitani N, Murakami K, Yamaura T, Ikeda T and Saiki I: Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma. Cancer Lett 165: 35-42, 2001.
162 Li XK, Motwani M, Tong W, Bornmann W and 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 58: 1287-1293, 2000.
163 Wang DY, Yeh CC, Lee JH, Hung CF and 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 27: 883-889, 2002.
164 Li M, Wu X and Xu XC: Induction of apoptosis by cyclooxygenase-2 inhibitor NS398 through a cytochrome C-dependent pathway in esophageal cancer cells. Int J Cancer 93: 218-223, 2001.
165 Nishihara H, Kizaka-Kondoh S, Insel PA and Eckmann L: Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2. Proc Natl Acad Sci U S A 100: 8921-8926, 2003.
166 Fujino H, Xu W and Regan JW: Prostaglandin E2 induced functional expression of early growth response factor-1 by EP4, but not EP2, prostanoid receptors via the phosphatidylinositol 3-kinase and extracellular signal-regulated kinases. J Biol Chem 278: 12151-12156, 2003.
167 Adams JM and Cory S: The Bcl-2 protein family: arbiters of cell survival. Science 281: 1322-1326, 1998.
168 Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91: 231-241, 1997.
169 Chao DT and Korsmeyer SJ: BCL-2 family: regulators of cell death. Annu Rev Immunol 16: 395-419, 1998.
170 Nicholson KM and Anderson NG: The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14: 381-395, 2002.
171 Qi C, Zhu Y and Reddy JK: Peroxisome proliferator-activated receptors, coactivators, and downstream targets. Cell Biochem Biophys 32 Spring: 187-204, 2000.
172 Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM and Evans RM: 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83: 803-812, 1995.
173 Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC and Lehmann JM: A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83: 813-819, 1995.
174 Fitzpatrick FA and Wynalda MA: Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro. J Biol Chem 258: 11713-11718, 1983.
175 He TC, Chan TA, Vogelstein B and Kinzler KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell. 99: 335-345, 1999.
176 Krishnan K and Brenner DE: Prostaglandin inhibitors and the chemoprevention of noncolonic malignancy. Gastroenterol Clin North Am 30: 981-1000, 2001.
177 Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM and Singer S: Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A 96: 3951-3956, 1999.
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