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系統識別號 U0007-0807201016470400
論文名稱(中文) 薑黃素及其結構類似物誘導人類乳癌細胞(MCF-7和MDA-MB-231)計畫性死亡之相關研究
論文名稱(英文) Studies on curcumin and its analogs on apoptotic activities in human breast adenocarcinoma cells (MCF-7 and MDA-MB-231)
校院名稱 臺北醫學大學
系所名稱(中) 生藥學研究所
系所名稱(英) Graduate Institute of Pharmacognosy
學年度 98
學期 2
出版年 99
研究生(中文) 江庭萱
研究生(英文) Ting-Hsuan Chiang
學號 M303097007
學位類別 碩士
語文別 中文
口試日期 2010-06-15
論文頁數 108頁
口試委員 指導教授-侯文琪
委員-傅淑玲
委員-李慶國
中文關鍵字 薑黃素  薑黃素結構類似物,  乳癌  細胞計畫性死亡 
英文關鍵字 curcumin  curcumin analog  breast cancer  apoptosis 
學科別分類
中文摘要 薑黃素 (curcumin)是植物薑黃 (turmeric)內主要具活性的成分,包含抗發炎、抗氧化、抗癌症轉移、誘導癌細胞執行細胞計畫性死亡等活性。本篇研究探討薑黃素及其二十三個結構類似物抑制兩株人類乳癌細胞 (MCF-7和MDA-MB-231)增生和誘導細胞計畫性死亡的相關機制。經由細胞存活率測試 (SRB assay),發現結構上具有多個甲氧基的結構類似物二號、六號、八十五號對於兩株乳癌細胞具有顯著毒性,且有濃度依存性、時間依存性的現象,不具細胞毒性之結構類似物九號被選做結構-活性探討之用。在5 μM濃度下,以雷射共軛焦顯微鏡觀察Annexin-V-FITC對於兩株乳癌細胞螢光染色,發現結構類似物六號螢光強度最強,顯示其phosphatidylserine (PS)外翻程度最高,表現出細胞計畫性死亡的特徵。以15 μM濃度處理乳癌細胞24小時,再以流式細胞儀分析Annexin-V-FITC/PI雙染之螢光比例,發現結構類似物六號對於兩株乳癌細胞誘導細胞計畫性死亡的比例將近100%﹔結構類似物二號誘導MDA-MB-231細胞株計畫性死亡達80%﹔結構類似物八十五號誘導MCF-7細胞株計畫性死亡達60%。在15 μM濃度下,探討薑黃素及結構類似物對於細胞週期的影響,發現薑黃素與結構類似物二號、六號、八十五號造成MCF-7細胞株G2/M期的停滯﹔薑黃素與結構類似物二號、八十五號造成MDA-MB-231細胞株G2/M期的停滯,結構類似物六號則造成G0/G1的停滯。結構類似物九號對於兩株乳癌細胞皆不造成細胞周期停滯。探討結構類似物六號對於細胞內活性氧化物 (reactive oxygen species; ROS)之影響,以濃度15 μM處理MDA-MB-231細胞株30分鐘,可顯著誘導細胞內ROS的表現;處理24小時後,細胞內Heme oxygenase-1 (HO-1)蛋白質表現顯著增加。結構類似物六號誘導caspase-9及caspase-3活化,經由細胞內途徑使MDA-MB-231細胞進行細胞計畫性死亡。此外,本研究中發現結構類似物六號有抑制癌症轉移的潛力,經由明膠酵素電泳法及畫痕試驗,結構類似物六號可顯著抑制MMP-9的活性及抑制MDA¬-MB-231細胞遷移。
英文摘要 Curcumin is the primary bioactive constituent of turmeric, which is an herbal medicine used in Asia for a long time. It has been shown to possess anti-inflammatory, antioxidant, anti-metastatic, and apoptosis- induced properties. In this study, curcumin and 23 different kinds of curcumin analogs were evaluated for cytotoxicity effects on two breast cancer cell lines—MCF-7 and MDA-MB-231. According to the results of cell viability assay, analog 2, 6 and 85 showed stronger growth inhibition activities in both MCF-7 and MDA-MB-231 cell lines than curcumin under concentration of 5 μM and were selected as test candidates. The analog 2, 6, and 85 together with negative control of analog 9 with four to six methoxyl substituents in the phenyl groups were chosen to compare structure-activity relationships. Apoptosis activity was examined by Annexin-V-FITC fluorescence stain by a confocal microscopy under 5 μM treatments. Among them, analog 6 was demonstrated to effectively induce apoptosis activity. By flow cytometry analysis for Annexin-V-FITC/PI fluorescence under concentration of 15 μM treatment for 24 hours, analog 6 showed almost 100% apoptosis in both MCF-7 and MDA-MB-231 cell lines; analog 2 induced 80% apoptosis in MDA-MB-231 cell line; analog 85 exhibited 80% apoptosis in MCF-7 cell line. Cell cycle distribution was arrested by curcumin, analog 2, 6, and 85 in G2/M phase in MCF-7 cells. In MDA-MB-231 cells, curcumin, analog 2, and 85 caused cell cycle arrest in G2/M phase; analog 6 caused cell cycle arrest in G0/G1 phase. Analog 9 showed no influence on cell cycle distribution in both cell lines. To study the mechanism of apoptosis induction by analog 6 and curcumin, cellular reactive oxygen species (ROS) produced levels were detected. It was found that curcumin and analog 6 elevated ROS levels in MDA-MB-231 cells after being treated with 30 minutes. Furthermore, curcumin and analog 6 for 24-h treatments induced heme oxygenase-1 (HO-1) protein expressions in both cell lines. Analog 6 increased MDA-MB-231 cells caspase-9 and caspase-3 actived form expression. We concluded that analog 6 induce MDA-MB-231 cells undergo apoptosis through intrinsic pathway. In addition, according to gelatin zymograhy and wound healing assay, analog 6 inhibits MDA-MB-231 cells migration through suppressing MMP-9 activity.
論文目次 緒論 …………………………………………….. 1
第一節 前言....................................1
第二節 文獻回顧................................2
(一) 薑黃素(curcumin)..…….......…...……….… 2
(二) 細胞計畫性死亡(apopotosis)…..….……..12
(三) 活性氧化物(Reactive oxygen species;ROS)..
…………………………………………….23
(四) 血紅素加氧酶 (Heme oxygenase)……….25
(五) 乳癌……………………………………….28
第二章 研究方法…………………………………………30
第一節 實驗材料………………………………………30
(一) 儀器……………………………………………30
(二) 試藥與耗材……………………………………31
(三) 抗體……………………………………………33
(四) 細胞株…………………………………………33
第二節 實驗方法…………………………………………39
第三章 結果 …………………………………………………49
1. 薑黃素及其二十三個結構類似物對於人類乳癌細胞(MCF-7及MDA-MB-231)之細胞毒性 ……………49
2. 不同濃度的薑黃素及其結構類似物(二號、六號、九號、八十五號)對於MCF-7及MDA-MB-231細胞株之細胞毒性 …………………………………………52
3. 薑黃素及其結構類似物(二號、六號、九號、八十五號)在不同處理時間對於MCF-7及MDA-MB-231細胞株之細胞存活率 …………………………………55
4. 薑黃素及其結構類似物(二號、六號、九號、八十五號)對於細胞計畫性死亡(Apoptosis)特徵:細胞膜內磷脂質外翻的影響 ……………………………………58
5. 以流式細胞儀分析薑黃素及其結構類似物(二號、六號、九號、八十五號)造成細胞計畫性死亡之程度..
……………………………………………………… 61
6. 薑黃素其結構類似物(二號、六號、九號、八十五號)對於細胞週期的影響 ………………………………66
7. 結構類似物六號誘導MDA-MB-231細胞內ROS產生 ……………………………………………………71
8. 薑黃素及其結構類似物六號對於HO-1蛋白質表現量的影響 ………………………………………………74
9. 抑制caspase活性對於結構類似物六號處理後細胞存活率之影響 …………………………………………77
10. 薑黃素及結構類似物六號誘導MDA-MB-231細胞 caspase-9活化 ……………………………………79
11. 利用酵素連結免疫吸附法 (ELISA)測定薑黃素及 結構類似物六號對於caspase-3活化態蛋白質表現之影響 …………………………………………… 82
12. 薑黃素及其結構類似物六號對於MDA-MB-231細 胞株MMP-9活性影響之試驗 ……………………84
13. 薑黃素及其結構類似物六號對於MDA-MB-231細胞株抑制遷移之試驗 …………………………………87
第四章 討論 …………………………………………………90
第一節 篩選誘導乳癌細胞計畫性死亡之薑黃素結構類似物……………………………………………90
第二節 薑黃素及結構類似物二號、六號、八十五號於細胞週期的影響………………………………93
第三節 薑黃素及結構類似物六號對於細胞內ROS的影響………………………………………………93
第四節 結構類似物六號誘導MDA-MB-231細胞進行計畫性死亡經由細胞內途徑……………………95
第五節 結構類似物六號具有抑制乳癌細胞遷移的活性………………………………………………96
第五章 結論…………………………………………………97
第六章 參考資料 …………………………………………98
參考文獻 Adams BK, Cai J, Armstrong J, Herold M, Lu YJ, Sun A, Snyder JP, Liotta DC, Jones DP, Shoji M (2005) EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anti-Cancer Drugs 16, 263-275

Adams J, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281, 1322-1326

Adams JM (2003) Ways of dying: multiple pathways to apoptosis. Genes & Development 17, 2481-2495

Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23, 363-398

Aggarwal BB, Shishodia S, Takada Y, Banerjee S, Newman RA, Bueso-Ramos CE, Price JE (2005) Curcumin suppresses the paclitaxel-induced nuclear factor-kappa B pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clinical Cancer Research 11, 7490-7498

Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007) Curcumin: the Indian solid gold. Adv. Exp. Med. Biol., 1-75

Aggarwal BB, Sung B (2008) Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends in Pharmacological Sciences 30, 85-94

Arbiser JL, Klauber N, Rohan R, van Leeuwen R, Huang MT, Fisher C, Flynn E, Byers HR (1998) Curcumin is an in vivo inhibitor of angiogenesis. Mol Med. 4, 376-383

Bachmeier BE, Nerlich AG, Iancu CM, Cilli M, Schleicher E, Vene R, Dell'Eva R, Jochum M, Albini A, Pfeffer U (2007) The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice. Cellular Physiology and Biochemistry 19, 137-152

Bava SV, Puliappadamba VT, Deepti A, Nair A, Karunagaran D, Anto RJ (2005) Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-kappa B and the serine/threonine kinase Akt and is independent of tubulin polymerization. Journal of Biological Chemistry 280, 6301-6308

Bicknell G, Snowden R, Cohen G (1994) Formation of high molecular mass DNA fragments is a marker of apoptosis in the human leukaemic cell line, U937. Journal of Cell Science 107, 2483-2489

Calabrese V, Bates TE, Mancuso C, Cornelius C, Ventimiglia B, Cambria MT, Renzo LD, Lorenzo AD, Dinkova-Kostova AT (2008) Curcumin and the cellular stress response in free radical-related diseases. Mol. Nutr. Food Res. 52, 1062-1073

Carey L, Dees E, Sawyer L (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin. Cancer Res. 13, 2329-2334

Chang HY, Yang X (2000) Protease for Cell Suicide: Functions and Regulation of Caspases. Microbiology and Molecular Biology Reviews 64, 821-846

Chen GG, Lai PBS (2009) Apoptosis in Carcinogenesis and Chemotherapy Apoptosis in Cancer. (Guildford Boulder: Springer London NetLibrary), pp xxii, 384 p.

Chen M, Wang J (2002) Initiator caspases in apoptosis signaling pathways. Apoptosis 7, 313-319

Chabottaux V, Noel A (2007) Breast cancer progression: insights into mutifaceted matrix metalloproteinases. Clin Exp Metastasis 24, 647-656

Chowdhury I, Tharakan B, Bhat G (2008) Caspases - an update. Comp Biochem Physiol B Biochem Mol Biol 151, 10-27

Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J. 326, 1-16

Diederich M (2003) Apoptosis : from signaling pathways to therapeutic tools. (New York: New York Academy of Sciences)
Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M, Diederich M (2005) Chemopreventive and therapeutic effects of curcumin. Cancer Letters 223, 181-190

Earnshaw W, Martins L, Kaufmann S (1999) Mammlian caspases. Annu. Rev. Biochem. 68, 383-424

Emens L, Davidson N (2004) Trastuzumab in breast cancer. Oncology (Huntingt) 18

Engeland Mv, Ramaekers F, Schutte B, Reutelingsperger C (1996) A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry 24, 131-139

Fadok V, Bratton D, Frasch SC, Warner M, Henson P (1998) The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death and Differentiation 5, 551-562

Fang J, Akaike T, Maeda H (2004) Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment. Apoptosis 9, 27-35

Fang J, Lu J, Holmgren A (2005) Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J. Biol. Chem. 280, 25284-25290

Fang J, Seki T, Maeda H (2009) Therapeutic strategies by modulating oxygen stress in cancer and inflammation. Advanced Drug Delivery Reviews 61, 290-302

Farombi EO, Surh YJ (2006) Heme oxygenase-1 as a potential therapeutic target for hepatoprotection. J Biochem Mol Biol 39, 479-491

Fuchs JR, Pandit B, Bhasin D, Etter JP, Regan N, Abdelhamid D, Li C, Lin J, Li P-K (2009) Structure-activity relationship studies of curcumin analogues. Bioorganic & Medicinal Chemistry Letters 19, 2065-2069

Garg AK, Buchholz TA, Aggarwal BB (2005) Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxidants & Redox Signaling 7, 1630-1647

Gattia R, Bellettib S, Orlandinic G, Bussolatib O, Dall'Astab V, Gazzolab GC (1998) Comparison of Annexin V and Calcein-AM as Early Vital Markers of Apoptosis in Adherent Cells by Confocal Laser Microscopy Journal of Histochemistry and Cytochemistry 46, 895-900

Goel A, Jhurani S, Aggarwal BB (2008a) Multi-targeted therapy by curcumin: how spicy is it ? Mol. Nutr. Food Res., 1010-1030

Goel A, Kunnumakkara AB, Aggarwal BB (2008b) Curcumin as "Curecumin": From kitchen to clinic. Biochemical Pharmacology 75, 787-809

Grutter M (2000) Caspases: key players in programmed cell death. Curr Opin Struct Biol. 10, 649-655

Hanahan D, Weinberg R (2000) The hallmarks of cancer. Cell 100, 57-70
Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: From ancient medicine to current clinical trials. Cell. Mol. Life Sci. 65, 1631-1652

Hengartner MO (2000) The biochemistry of apoptosis. Nature 407, 770-776

Hill M, Pereira V, Chauveau C, Zagani R, Remy Sv, Tesson L, Mazal D, Ubillos L, Brion Rg, Ashgar K, Mashreghi MF, Kotsch K, Moffett J, Doebis C, Seifert M, Boczkowski J, Osinaga E, Anegon I (2005) Heme oxygenase-1 inhibits rat and human breast cancercell proliferation: mutual cross inhibition with indoleamine 2,3-dioxygenase. FASEB J .19, 1957-1968

Hahm ER, Gho YS, Park S, Park C, Kim KW, Yang CH (2004) Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis. Biochem Biophys Res Commun 321: 337-44

Hu W, Kavanagh JJ (2003) Anticancer therapy targeting the apoptotic pathway. The Lancet Oncology 4, 721-729

Igney F, Krammer P (2002) Death and Anti-death: Tumor Resistance to apoptosis. Nature Reviews 2, 277-288

Jeong GS, Oh GS, Pae HO, Jeong SO, Kim YC, Shin MK, Seo BY, Han SY, Lee HS, Jeong JG, Koh JS, Chung HT (2006) Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: ortho-methoxy groups are essential to enhance heme oxygenase activity and protection. Exp Mol Med 38, 393-400

Jozkowicz A, Was H, Dulak J (2007) Heme Oxygenase-1 in Tumors: Is It a False Friends? Antioxid Redox Signal. 9, 2099-2118

Karunagaran D, Rashmi R, Kumar TRS (2005) Induction of apoptosis by curcumin and its implications for cancer therapy. Current Cancer Drug Targets 5, 117-129

Kerr J, Wyllie A, Currie A (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26, 239-571

Khan N, Afaq F, Mukhtar H (2008) Cancer chemoprevention through dietary antioxidants: Progress and promise. Antioxidants & Redox Signaling 10, 475-510

Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri E, Baehrecke E, Blagosklonny M, El-Deiry W, Golstein P, Green D, Hengartner M, Knight R, Kumar S, Lipton S, Malorni W, Nuñez G, Peter M, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G (2008) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16, 3-11

Krysko TV (2008) Apoptosis and necrosis: Detection, discrimination and phagocytosis. Methods 44, 205-221

Kumar S (1998a) Apoptosis : biology and mechanisms. (Berlin ; New York: Springer)

Kumar S (1998b) Apoptosis : mechanisms and role in disease. (Berlin ; New York: Springer)

Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini K (2008) Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochem Biophys Acta. 1780, 673-679

Kuttan G, Kumar KBH, Guruvayoorappan C, Kuttan R (2007) Antitumor, anti-invasion, and antimetastatic effects of curcumin. Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease 595, 173-184

Lawen A (2003) Apoptosis- an introduction. BioEssays 25, 888-896

Lee J, Surh Y (2005) Nrf2 as a novel molecular target for chemoprevention. Cancer Lett. 224, 171-184

Levy OA, Malagelada C, Greene LA (2009) Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps Apoptosis 14, 478-500

Li L, Aggarwal BB, Shishodia S, Abbruzzese J, Kurzrock R (2004) Nuclear factor-kappa B and I kappa B kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer 101, 2351-2362

Li M, Zhang Z, Hill DL, Wang H, Zhang RW (2007) Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. Cancer Research 67, 1988-1996

Limtrakul P (2007) Curcumin as chemosensitizer. Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease 595, 269-300

Lin C-W, Shen S-C, Hou WC, Yang L-Y, Chen Y-C (2008) Heme oxygenase-1 inhibits breast cancer invasion via suppressing the expression of matrix metalloproteinase-9. Mol Cancer Ther May 7; 1195 7, 1195-1206

Lin L, Hutzen B, Ball S, Foust E, Sobo M, Deangelis S, Pandit B, Friedman L, Li C, Li P-K, Fuchs J, Lin J (2009) New curcumin analogues exhibit enhanced growth-suppressive activity and inhibit AKT and signal transducer and activator of transcription 3 phosphorylation in breast and prostate cancer cells. Cancer Science 100, 1719-1727

Lin L, Shi Q, Nyarko AK, Bastow KF, Wu C-C, Su C-Y, Shih CC-Y, Lee K-H (2006) Antitumor Agents. 250.† Design and Synthesis of New Curcumin Analogues as Potential. Anti-Prostate Cancer Agents. J. Med. Chem 49, 3963-3972

Liu Q, Loo WTY, Sze SCW, Tong Y (2009) Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NF kappa B, cyclinD and MMP-1 transcription. Phytomedicine 16, 916-922

Lopez-Lazaro M (2008) Anticancer and carcinogenic properties of curcumin: Consideration for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol. Nutr. Food Res. 52, S103-S127

Maines M (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J . 2, 2557-2568

Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, Schie RCv, LaFace DM, Green DR (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. . Journal of expermental medicine 182, 1545-1556

Mignotte B, Vayssiere J-L (1998) Mitochondria and apoptosis. European Journal of Biochemistry 252, 1-15

Milhas D, Cuvillier O, Therville N, Clavé P, Thomsen M, Levade T, Benoist H, Ségui B (2005) Caspase-10 Triggers Bid Cleavage and Caspase Cascade Activation in FasL-induced Apoptosis. The Journal of Biological Chemistry 280, 19836-19842

Mosley CA, Liotta DC, Snyder JP (2007a) Highly active anticancer curcumin analogues. Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease 595, 77-103

Mosley CA, Liotta DC, Snyder JP, eds. (2007b) HIGHLY ACTIVE ANTICANCER CURCUMIN ANALOGUES (Springer US)

Nunez R (2001) DNA Measurement and Cell Cycle Analysis
by Flow Cytometry. Curr. Issues Mol. Biol. 3, 67-70

Pae HO, Jeong SO, Kim HS, Kim SH, Song YS, Kim SK, Chai KY, Chung HT (2008) Dimethoxycurcumin, a synthetic curcumin analogue with higher metabolic stability, inhibits NO production, inducible NO synthase expression and NF-kappaB activation in RAW264.7 macrophages activated with LPS. Mol Nutr Food Res

Pan J-S, Hong M-Z, Ren J-L (2009) Reactive oxygen species: A double-edged sword in oncogenesis. World Gastroenterol 15, 1702-1707

Poorichaya S, Chada P, Somjai N, Supeenun U, Phumala MN (2007) Comparative Antioxidant Activities of Curcumin and Its Demethoxy and Hydrogenated Derivatives. Biol Pharm Bull 30, 74-78

Ravindran J, Prasad S, Aggarwal BB (2009) Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively? Aaps Journal 11, 495-510

Reuter S, Eifes S, Dicato M, Aggarwal BB, Diederich M (2008) Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochemical Pharmacology 76, 1340-1351

Riedl S, Shi Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 5, 897-907

Rodriguez L, Wu X, Guan J (2005) Wound-healing assay. Methods Mol Biol. 294, 23-29

Russo I, Russo J (1998) Role of hormones in mammary cancer initiation and progression. J Mammary Gland Biol Neoplasia 3, 433-439

Schlotter CM, Vogt U, Allgayer H, Brandt B (2008) Molecular targeted therapies for breast cancer treatment. Breast Cancer Research 10, 211-222

Schumacker, T. P (2006) Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell 10, 175-176

Sharma RA, Gescher AJ, Steward WP (2005) Curcumin: The story so far. European Journal of Cancer 41, 1955-1968

Shimohama S (2000) Apoptosis in Alzheimer's disease—an update Apoptosis 5, 9-16

Shishodia S, Singh T, Chaturvedi MM (2007) Modulation of transcription factors by curcumin. Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease 595, 127-148

Simon A, Allais DP, Duroux JL, Basly JP, Durand-Fontanier S, Delage C (1998) Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships. Cancer Lett 129, 111-116

Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. (Springer), pp 415-418

Singh S, Aggarwal BB (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) J Biol Chem, 24995-25000

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W (1987) Human Breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177-182

Smith J, Weidemann M (1993) Further characterization of the neutrophil oxidative burst by flow cytometry. . J Immunol Methods 162, 261-268

Smith PK, et al. (1985) Measurement of protein using bicinchoninic acid
Anal. Biochem. 150, 76-85

Sprick MR, Riseser E, Stahl H, Gross-Wilde A, Weigand MA, Walczak H (2002) Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. The EMBO Journal 21, 4520-4530

Stennicke HR, Salvesen GS (1998) Properties of the caspases. Biochimica et Biophysica Acta 1387, 17-31

Strimpakos AS, Sharma RA (2008) Curcumin: Preventive and Therapeutic Properties in Laboratory Studies and Clinical Trials. Antioxidants & Redox Signaling 10, 511-545

Sullivan A (1989) Selected biochemical techniques as applied to immunology. Curr Opin Immunol. 5, 966-970

Surh Y, Kundo J, Na H, Lee J (2005) Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J Nutr. 135, 2993S-3001S

Surh YJ, Chun KS (2007) Cancer chemopreventive effects of curcumin. Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease 595, 149-172

Syng-ai C, Kumari AL, Khar A (2004) Effect of curcumin on normal and tumor cells: Role of glutathione and bcl-2. Molecular Cancer Therapeutics 3, 1101-1108

Tamvakopoulos C, Dimas K, Sofianos ZD, Hatziantoniou S, Han Z, Liu ZL, Wyche JH, Pantazis P (2007) Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin. Clin Cancer Res 13, 1269-1277

Tenhunen R, Marver H, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Nat Acad Sci 61, 748-755

Toth M, Fridman R (2008) Assessment of Gelatinases (MMP-2 and MMP-9 by Gelatin Zymography. Metastasis Research Protocols 57, 163-174

Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature Reviews Drug Discovery 8, 579-591

Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions 160, 1-40

Vichai V, Kirtikara K (2006) Sulforhodamine B colorimetric assay for cytotoxicity. Nature Protocols 1, 1112-1116

Wang J, Chun HJ, Wong W, Spencer DM, Lenardo MJ (2001) Caspase-10 is an initiator caspase in death receptor signaling. PNAS 98, 13884-13888

Wyllie A, Kerr J, Currie A (1980) Cell death: the significance of apoptosis. Int. Rev. Cytol. 68, 251-306

Zhao JJ, Silver DP (2009) Estrogen Receptor-Negative Breast Cancer: New Insights into Subclassification and Targeting. Clin Cancer Res. 15, 6309-6310
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