博碩士論文 104827603 詳細資訊




以作者查詢圖書館館藏 以作者查詢臺灣博碩士 以作者查詢全國書目 勘誤回報 、線上人數:23 、訪客IP:3.239.109.55
姓名 潘蒂亞(Pham Thi Tuyet)  查詢紙本館藏   畢業系所 生醫科學與工程學系
論文名稱
(Synthesis, Spectral Characterization and Evaluation of Quercetin-Zinc Complex for Tumoricidal and Anti-metastasis of Human Bladder Cancer Cell)
相關論文
★ 研究探討層流剪應力於高糖環境下對膀胱癌細胞遷移與侵襲行為之影響★ 研究探討層流剪應力對泌尿上皮細胞癌於細胞週期運作之影響與機轉
★ 設計並建構一全氟碳光生物反應器組用於分離混合氣體中之二氧化碳並同時提升微藻養殖及其經濟產物生成之效能★ 包覆靛氰綠與喜樹鹼之標靶全氟碳奈米乳劑 研製於強化乳癌螢光擴散光學影像暨 光/化學治療之研究
★ 研製包覆靛氰綠與絲裂黴素C之標靶全氟碳奈米乳劑應用於膀胱癌光-化學治療之研究★ 研製包覆靛氰綠及利福平之聚乳酸-聚甘醇酸奈米粒子用於破壞生物膜之抗菌治療
★ 可動態改變外翻力矩的治療退化性膝關節炎輔具★ 聚乙二醇對於擬球藻生長與脂質堆積之影響
★ 製備包覆靛氰綠及阿黴素之聚乳酸甘醇酸-聚乙二醇交聯標靶奈米粒子用於乳癌光/化學治療之研究★ 研製包覆靛氰綠與阿黴素之標靶氟化奈米乳劑用於乳癌光/化學治療之研究
★ 研究設計全氟碳化物光生物反應器系統用以純化沼氣並藉此提升微藻生物質及生質能源之產量★ 針對糖尿病足潰瘍設計並製作一種抗菌且能促進傷口癒合的甲殼素複合式水凝膠之研究
★ 利用PLGA微球載體結合超聲波駐波場以提高巨噬細胞藥物輸送之效率★ 以血流動力系統探討血管內皮細胞在尼古丁刺激下對層流剪應力之型態異常與自體凋亡之表現變化
★ 以板式流道系統模擬血管內皮細胞於層流剪力影響下受尼古丁刺激產生發炎反應之研究★ 結合超聲波駐波場與層堆疊自體組裝微球載體建構提高分子傳遞至細胞內效率之方法
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 ( 永不開放)
摘要(中) 膀胱癌是泌尿道最常見的癌症之一,男性罹患癌症機率比女性多三倍。每年死於膀胱的患者數量都在增加。由於癌症具有轉移的能力,因此治療癌症並不容易。儘管手術技術的進步和全身化療的改善,膀胱癌的5年存活率沒有改變。為了要克服上述的所有困難,所以尋找抗癌和抗轉移的新藥是迫切需要的。在這個研究中,槲皮素˗鋅復合 (quercetin-Zn) 被發現,它不僅具有濳在的抗癌特性,而且能夠有效抑制膀胱癌細胞的遷移、侵襲和轉移。槲皮素(quercetin) 是最具生物活性的黃酮類合物之一,有在許多水果,蔬菜和飲料。由於其抗癌,抗氧化和抗發炎效果,因此槲皮素被作為化學藥物研究應用在各種癌症。然而,槲皮素很難被吸收到生物體內,因此導致生物利用度差。有趣的是,槲皮素能與金屬配位以形成複合物並增強其生物利用度,並改變體內傳遞槲皮素的方式。槲皮素˗鋅復合的抗癌活性已被證明,因此,槲皮素˗鋅複合物是癌症治療藥物中具有前景的藥物。然而,槲皮素˗鋅對腫瘤細胞的抑制作用並沒有完全瞭解。槲皮素屬於廣泛類型的酚類化合物,酚類化合物已被報導作為對癌症侵襲和轉移的潛在抑制作用,因此認為槲皮素˗鋅複合物也具有這種性質。在這項研究中,合成了槲皮素˗鋅,其化學性質顯示在UV-VIS,FT-IR,1H-NMR,表明通過3-OH 和C4=0 基團的結合位點。比較了槲皮素˗鋅,槲皮素和鋅離子對BFTC-905和NIH-3T3 細胞的抗癌作用。對BFTC-905細胞的細胞毒性測試結果表明,槲皮素˗鋅殺傷作用比單獨槲皮素高2.8倍。且在NIH-3T3細胞上也發現有相同作用,槲皮素˗鋅對NIH-3T3細胞的細胞毒性比單獨使用槲皮素較高。此外鋅離子對BFTC-905和NIH-3T3細胞都是無毒的。進一步的研究發現了槲皮素˗鋅抗轉移作用在BFTC-905細胞在非細胞毒性濃度(0-50μM)下。在此範圍中,用槲皮素-鋅處理的BFTC-905細胞通過傷口癒合測試明顯地顯示濃度上升時細胞遷移能力降低。基於侵犯測試結果經槲皮素-鋅複合物處理24 h後,顯著侵入膜下側的BFTC-905細胞與對照組相比降低(p值<0.05),提示BFTC-905細胞用槲皮素-鋅複合物處理顯示顯著減少侵犯能力。此外為了研究槲皮素-鋅複合物的抗轉移機制,檢測了AKT和MT1-MMP的表達。 我們發現,p-AKT和MT1-MMP水平的表達下調槲皮素鋅處理的BFTC-905細胞。 最重要的,這些研究提供更好的方式去了解槲皮素-鋅複合物的分子途徑抑制轉移和侵犯可能是治療膀胱癌有用的方式。
摘要(英) Bladder cancer is one of the most frequent cancer of urinary tract and it’s nearly three time more common in men than women. The patients died of bladder cancer increase every year. It could be the effective treatments for tumors are not easy to achieve due to existence of metastases, tumor metastases mainly leads to high mortality rate of bladder cancer patients. In spite of advances in surgical techniques and improvements of systemic chemotherapies, there has been no change in the 5-year survival rate of bladder cancer. To overcome all these difficulties above, looking for a new drug is pressing need, which should be antitumor and anti-metastasis activities. In this research, quercetin-zinc (quercetin-Zn) was found that, it possessed not only potent anticancer activity, but was also able to effectively inhibit migration, invasion and metastasis of human bladder cancer cells (BFTC-905). Quercetin is one of the most bioactive flavonoids compound and present in many fruits, vegetables, beverages. Due to its anticancer, anti-oxidant and anti-inflammation activity, quercetin has been studied extensively as a chemoprevention agent in variety cancer models. However, quercetin was found to be difficult absorbed into the body, thus resulted in poor bioavailability. Interestingly, quercetin is the ideally compound for coordinate with metal to form a complex compound and enhance its biological activity with increasing bioavailability and also change the way deliver quercetin in vivo. The anticancer activity of quercetin-Zn complex has been demonstrated, therefore, quercetin-Zn is a promising complex in developing new medicine for cancer treatment. However, many aspects of the inhibitory effects of quercetin-Zn to tumor cells are not still completely understood. Quercetin is belong to extensive class of phenolic compounds, phenolic compounds have been report as a potential inhibitory effect on cancer invasion and metastasis, thus, it is believed that quercetin-Zn complex also own this property. In this work, quercetin-Zn was synthesized and its chemical properties were characterized by UV-VIS, FT-IR, 1H NMR, which showed that binding site via 3-OH and C4=O group. The anticancer effects of quercetin-Zn, quercetin and zinc ion on BFTC-905 and NHI-3T3 cells were compared. The result of cell viability on BFTC-905 cells demonstrated that killing effect was 2.8 time higher than quercetin alone. However, this effect was also found on NIH-3T3 cells, cytotoxic effect of quercetin-Zn on NIH-3T3 cells was shown to be higher than quercetin alone. In contrast, zinc ion was found to be non-toxic to both BFTC-905 and NIH-3T3 cells. Further investigation revealed the anti-metastasis effect of quercetin-Zn on BFTC-905 cells under non-cytotoxic concentration. In non-cytotoxic concentration range (0-50µM), BFTC-905 cells that were treated with quercetin-Zn significantly exhibited a concentration-dependent reduction in cell migration by wound healing assay. Based on the invasion assay result, after 24 h treatment with quercetin-Zn complex, the amount of BFTC-905 cells that invaded to the lower side of the membrane markedly reduced compare with control (p-value<0.05), suggested that BFTC-905 cells were treated with quercetin-Zn complex display significant reduction in invasive capacity. Furthermore, in order to investigate the anti-metastasis mechanism of quercetin-Zn complex, the expression of AKT and MT1-MMP were examined. We found that, the expression of p-AKT and MT1-MMP level were down-regulated in quercetin-Zn-treated BFTC-905 cells. Importantly, these findings provide better understanding for the molecular pathway of quercetin-Zn complex on suppression of migration and invasion which might be useful as a therapeutic strategy to treat human bladder cancer.
關鍵字(中) ★ 膀胱癌
★ 抗癌
★ 抗轉移
★ 槲皮素
★ 鋅
關鍵字(英)
論文目次 CONTENT
摘要 I
Abstract III
Acknowledgement VI
List of Figure X
List of Table XIII
Chapter 1 Introduction 1
Chapter 2 Literature Review 5
2.1 Bladder Cancer 5
2.2 Bladder Cancer Metastasis 7
2.3 Flavonoid-Metal Complex 8
2.3.1 Quercetin 10
2.3.2 Zinc Ion 11
2.4 Molecular Mechanism 12
2.4.1 Protein Kinase B (AKT) 12
2.4.2 Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) 13
Chapter 3 Materials and Method 16
3.1 Experimental Materials 16
3.1.1 Experimental Devices 16
3.1.2 Cell Culture 16
3.1.3 Drugs and Reagents 17
3.2 Experimental Method: Quercetin-Zn Complex Synthesis 19
3.3 Cytotoxicity Assay 21
3.4 Examination of Cell Motility 21
3.4.1 Wound Healing Assay 21
3.4.2 Invasion Assay 21
3.5 Western Blotting 25
3.5.1 Sample Preparation 25
3.5.2 Protein Concentration Determination 25
3.5.3 SDS-Gel Preparation 25
3.5.4 Electrophoresis Preparation 26
3.5.5 Protein Transfer 26
3.5.6 Antibody Incubation 26
3.5.7 Imaging and Data Analysis 27
Chapter 4 Results and Discussion 28
4.1 Fourier Transform Infrared Spectroscopy (FT-IR) 28
4.2 Ultraviolet-Visible Spectroscopy (UV-VIS) 32
4.3 Proton Nuclear Magnetic Resonance (NMR) Spectroscopy 35
4.4 Cytotoxicity of Compounds 37
4.5 Migratibility of Cell with Quercetin-Zn 44
4.6 Invasiveness of Cells with Quercetin-Zn Complex 47
4.7 Molecular Pathway Investigation 49
Chapter 5 Conclusion 56
Chapter 6 Future Works 58
References 59

參考文獻 1. Andreassen, B., B. Aagnes, R. Gislefoss, M. Andreassen, and R. Wahlqvist, Incidence and Survival of urothelial carcinoma of the urinary bladder in Norway 1981-2014. BMC cancer, 2016. 16(1): p. 799.
2. Society, A.C., Cancer Facts & Figures 2017. 2017, American Cancer Society Atlanta, GA.
3. Chiang, C.-J., W.-C. Lo, Y.-W. Yang, S.-L. You, C.-J. Chen, and M.-S. Lai, Incidence and survival of adult cancer patients in Taiwan, 2002–2012. Journal of the Formosan Medical Association, 2016. 115(12): p. 1076-1088.
4. Hung, C.-F., C.-K. Yang, and Y.-C. Ou, Urologic cancer in Taiwan. Japanese journal of clinical oncology, 2016. 46(7): p. 605-609.
5. Sherif, A., M.N. Jonsson, and N.P. Wiklund, Treatment of muscle-invasive bladder cancer. Expert review of anticancer therapy, 2007. 7(9): p. 1279-1283.
6. Heney, N., Natural history of superficial bladder cancer. Prognostic features and long-term disease course. The Urologic clinics of North America, 1992. 19(3): p. 429-433.
7. Nirmal, J., Y.-C. Chuang, P. Tyagi, and M.B. Chancellor, Intravesical therapy for lower urinary tract symptoms. Urological Science, 2012. 23(3): p. 70-77.
8. Rajaganapathy, B.R., M.B. Chancellor, J. Nirmal, L. Dang, and P. Tyagi, Bladder uptake of liposomes after intravesical administration occurs by endocytosis. PloS one, 2015. 10(3): p. e0122766.
9. Ndagi, U., N. Mhlongo, and M.E. Soliman, Metal complexes in cancer therapy–an update from drug design perspective. Drug design, development and therapy, 2017. 11: p. 599.
10. Bastian, A., J.E. Thorpe, B.C. Disch, L.C. Bailey-Downs, A. Gangjee, R.K. Devambatla, J. Henthorn, K.M. Humphries, S.S. Vadvalkar, and M.A. Ihnat, A small molecule with anticancer and antimetastatic activities induces rapid mitochondrial-associated necrosis in breast cancer. Journal of Pharmacology and Experimental Therapeutics, 2015. 353(2): p. 392-404.
11. Tsai, J.-R., P.-L. Liu, Y.-H. Chen, S.-H. Chou, Y.-J. Cheng, J.-J. Hwang, and I.-W. Chong, Curcumin inhibits non-small cell lung cancer cells metastasis through the Adiponectin/NF-κb/MMPs signaling pathway. PloS one, 2015. 10(12): p. e0144462.
12. Shen, C.H., J.J. Shee, J.Y. Wu, Y.W. Lin, J.D. Wu, and Y.W. Liu, Combretastatin A‐4 inhibits cell growth and metastasis in bladder cancer cells and retards tumour growth in a murine orthotopic bladder tumour model. British journal of pharmacology, 2010. 160(8): p. 2008-2027.
13. Mei, L., Y. Liu, H. Zhang, Z. Zhang, H. Gao, and Q. He, Antitumor and antimetastasis activities of heparin-based micelle served as both carrier and drug. ACS applied materials & interfaces, 2016. 8(15): p. 9577-9589.
14. von der Maase, H., S. Hansen, J. Roberts, L. Dogliotti, T. Oliver, M. Moore, I. Bodrogi, P. Albers, A. Knuth, and C. Lippert, Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. Journal of clinical oncology, 2000. 18(17): p. 3068-3077.
15. Zhang, X.-A., S. Zhang, Q. Yin, and J. Zhang, Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway. Pharmacognosy magazine, 2015. 11(42): p. 404.
16. Luo, C.-l., Y.-q. Liu, P. Wang, C.-h. Song, K.-j. Wang, L.-p. Dai, J.-y. Zhang, and H. Ye, The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression. Biomedicine & Pharmacotherapy, 2016. 82: p. 595-605.
17. Gao, X., B. Wang, X. Wei, K. Men, F. Zheng, Y. Zhou, Y. Zheng, M. Gou, M. Huang, and G. Guo, Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer. Nanoscale, 2012. 4(22): p. 7021-7030.
18. Durgo, K., I. Halec, I. Šola, and J. Franekić, Cytotoxic and genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells in vitro. Archives of Industrial Hygiene and Toxicology, 2011. 62(3): p. 221-227.
19. Dolatabadi, J.E.N., A. Mokhtarzadeh, S.M. Ghareghoran, and G. Dehghan, Synthesis, characterization and antioxidant property of quercetin-Tb (III) complex. Advanced pharmaceutical bulletin, 2014. 4(2): p. 101.
20. Bravo, A. and J.R. Anacona, Metal complexes of the flavonoid quercetin: antibacterial properties. Transition Metal Chemistry, 2001. 26(1): p. 20-23.
21. Cornard, J. and J. Merlin, Spectroscopic and structural study of complexes of quercetin with Al (III). Journal of Inorganic Biochemistry, 2002. 92(1): p. 19-27.
22. Yamashita, N., H. Tanemura, and S. Kawanishi, Mechanism of oxidative DNA damage induced by quercetin in the presence of Cu (II). Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1999. 425(1): p. 107-115.
23. Li, Y., J. Yao, C. Han, J. Yang, M.T. Chaudhry, S. Wang, H. Liu, and Y. Yin, Quercetin, inflammation and immunity. Nutrients, 2016. 8(3): p. 167.
24. Lee, S.R., S.J. Noh, J.R. Pronto, Y.J. Jeong, H.K. Kim, I.S. Song, Z. Xu, H.Y. Kwon, S.C. Kang, and E.-H. Sohn, The critical roles of zinc: beyond impact on myocardial signaling. The Korean Journal of Physiology & Pharmacology, 2015. 19(5): p. 389-399.
25. Tan, J., B. Wang, and L. Zhu, DNA binding, cytotoxicity, apoptotic inducing activity, and molecular modeling study of quercetin zinc (II) complex. Bioorganic & medicinal chemistry, 2009. 17(2): p. 614-620.
26. Knowles, M.A. and C.D. Hurst, Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nature Reviews Cancer, 2015. 15(1): p. 25-41.
27. Cheung, G., A. Sahai, M. Billia, P. Dasgupta, and M.S. Khan, Recent advances in the diagnosis and treatment of bladder cancer. BMC medicine, 2013. 11(1): p. 13.
28. Babjuk, M., W. Oosterlinck, R. Sylvester, E. Kaasinen, A. Böhle, J. Palou-Redorta, and M. Rouprêt, EAU guidelines on non–muscle-invasive urothelial carcinoma of the bladder, the 2011 update. European urology, 2011. 59(6): p. 997-1008.
29. Ghervan, L., A. Zaharie, B. Ene, and F.I. Elec, Small-cell carcinoma of the urinary bladder: where do we stand? Clujul Medical, 2017. 90(1): p. 13.
30. Kim, S.-A., S.-M. Kwon, J.-A. Kim, K.W. Kang, J.-H. Yoon, and S.-G. Ahn, 5′-Nitro-indirubinoxime, an indirubin derivative, suppresses metastatic ability of human head and neck cancer cells through the inhibition of Integrin β1/FAK/Akt signaling. Cancer letters, 2011. 306(2): p. 197-204.
31. Sagiv, S., Great inventions that trick nature, new delivery system optimises bladder cancer treatment by increasing dwell time. ON drug Delivery, 2013.
32. Lu, Z., T.-K. Yeh, J. Wang, L. Chen, G. Lyness, Y. Xin, M.G. Wientjes, V. Bergdall, G. Couto, and F. Alvarez-Berger, Paclitaxel gelatin nanoparticles for intravesical bladder cancer therapy. The Journal of urology, 2011. 185(4): p. 1478-1483.
33. Bochner, B.H., D.D. Sjoberg, and V.P. Laudone, A randomized trial of robot-assisted laparoscopic radical cystectomy. New England Journal of Medicine, 2014. 371(4): p. 389-390.
34. Wan, L., K. Pantel, and Y. Kang, Tumor metastasis: moving new biological insights into the clinic. Nature medicine, 2013. 19(11): p. 1450-1464.
35. Jungwirth, U., C.R. Kowol, B.K. Keppler, C.G. Hartinger, W. Berger, and P. Heffeter, Anticancer activity of metal complexes: involvement of redox processes. Antioxidants & redox signaling, 2011. 15(4): p. 1085-1127.
36. Kasprzak, M.M., A. Erxleben, and J. Ochocki, Properties and applications of flavonoid metal complexes. RSC Advances, 2015. 5(57): p. 45853-45877.
37. Mueller, J., A. Schrader, M. Schrader, T. Schnoeller, and F. Jentzmik, Management of muscle-invasive bladder cancer. Minerva urologica e nefrologica= The Italian journal of urology and nephrology, 2013. 65(4): p. 235-248.
38. Primikyri, A., G. Mazzone, C. Lekka, A.G. Tzakos, N. Russo, and I.P. Gerothanassis, Understanding zinc (II) chelation with quercetin and luteolin: a combined NMR and theoretical study. The Journal of Physical Chemistry B, 2014. 119(1): p. 83-95.
39. Williams, R.J., J.P. Spencer, and C. Rice-Evans, Flavonoids: antioxidants or signalling molecules? Free radical biology and medicine, 2004. 36(7): p. 838-849.
40. Galati, G. and P.J. O′brien, Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radical Biology and Medicine, 2004. 37(3): p. 287-303.
41. López-Lázaro, M., Distribution and biological activities of the flavonoid luteolin. Mini reviews in medicinal chemistry, 2009. 9(1): p. 31-59.
42. Afanas′ ev, I.B., A.I. Dcrozhko, A.V. Brodskii, V.A. Kostyuk, and A.I. Potapovitch, Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. Biochemical pharmacology, 1989. 38(11): p. 1763-1769.
43. Liu, Y., K. Deng, J. Li, S. Liu, and S. Yao, Investigation of double stranded DNA damage induced by quercetin–copper (II) using piezoelectric quartz crystal impedance technique and potentiometric stripping analysis. Biophysical chemistry, 2004. 112(1): p. 69-76.
44. Hegde, A.H., S. Prashanth, and J. Seetharamappa, Interaction of antioxidant flavonoids with calf thymus DNA analyzed by spectroscopic and electrochemical methods. Journal of pharmaceutical and biomedical analysis, 2012. 63: p. 40-46.
45. Materska, M. and I. Perucka, Antioxidant activity of the main phenolic compounds isolated from hot pepper fruit (Capsicum annuum L.). Journal of Agricultural and Food Chemistry, 2005. 53(5): p. 1750-1756.
46. Vogiatzoglou, A., A.A. Mulligan, M.A. Lentjes, R.N. Luben, J.P. Spencer, H. Schroeter, K.-T. Khaw, and G.G. Kuhnle, Flavonoid intake in European adults (18 to 64 years). PloS one, 2015. 10(5): p. e0128132.
47. Nishimuro, H., H. Ohnishi, M. Sato, M. Ohnishi-Kameyama, I. Matsunaga, S. Naito, K. Ippoushi, H. Oike, T. Nagata, and H. Akasaka, Estimated daily intake and seasonal food sources of quercetin in Japan. Nutrients, 2015. 7(4): p. 2345-2358.
48. Jeong, J.H., J.Y. An, Y.T. Kwon, J.G. Rhee, and Y.J. Lee, Effects of low dose quercetin: Cancer cell‐specific inhibition of cell cycle progression. Journal of cellular biochemistry, 2009. 106(1): p. 73-82.
49. Yang, J.-H., T.-C. Hsia, H.-M. Kuo, P.-D.L. Chao, C.-C. Chou, Y.-H. Wei, and J.-G. Chung, Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis. Drug Metabolism and Disposition, 2006. 34(2): p. 296-304.
50. Choi, J.-A., J.-Y. Kim, J.-Y. Lee, C.-M. Kang, H.-J. Kwon, Y.-D. Yoo, T.-W. Kim, Y.-S. Lee, and S.-J. Lee, Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. International journal of oncology, 2001. 19(4): p. 837-844.
51. Yoshizumi, M., K. Tsuchiya, K. Kirima, M. Kyaw, Y. Suzaki, and T. Tamaki, Quercetin inhibits Shc-and phosphatidylinositol 3-kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells. Molecular Pharmacology, 2001. 60(4): p. 656-665.
52. Bors, W., C. Michel, and M. Saran, [41] Flavonoid antioxidants: Rate constants for reactions with oxygen radicals. Methods in enzymology, 1994. 234: p. 420-429.
53. da Silva, E.L., M.K. Piskula, N. Yamamoto, J.-H. Moon, and J. Terao, Quercetin metabolites inhibit copper ion‐induced lipid peroxidation in rat plasma. FEBS letters, 1998. 430(3): p. 405-408.
54. Song, Y., S.W. Leonard, M.G. Traber, and E. Ho, Zinc deficiency affects DNA damage, oxidative stress, antioxidant defenses, and DNA repair in rats. The Journal of nutrition, 2009. 139(9): p. 1626-1631.
55. Murakami, M. and T. Hirano, Intracellular zinc homeostasis and zinc signaling. Cancer science, 2008. 99(8): p. 1515-1522.
56. Soldatović, T., E. Selimović, and B. Ličina, Antibacterial activity of zinc (II) and copper (II) terpyridine complexes.
57. Sakurai, H., A. Katoh, T. Kiss, T. Jakusch, and M. Hattori, Metallo–allixinate complexes with anti-diabetic and anti-metabolic syndrome activities. Metallomics, 2010. 2(10): p. 670-682.
58. Milosavljevic, V., Y. Haddad, M.A.M. Rodrigo, A. Moulick, H. Polanska, D. Hynek, Z. Heger, P. Kopel, and V. Adam, The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy. PloS one, 2016. 11(10): p. e0163983.
59. Zishen, W., G. Ziqi, and Y. Zhenhuan, Synthesis, characterization and anticancer activity of L-alanine Schiff base complexes of copper (II), zinc (II), nickel (II) and cobalt (II). Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, 1990. 20(3): p. 335-344.
60. Mahmud, T., R. Rehman, A. Gulzar, A. Khalid, J. Anwar, U. Shafique, and M. Salman, Synthesis, characterization and study of antibacterial activity of enaminone complexes of zinc and iron. Arabian Journal of Chemistry, 2010. 3(4): p. 219-224.
61. Kowol, C.R., R. Trondl, V.B. Arion, M.A. Jakupec, I. Lichtscheidl, and B.K. Keppler, Fluorescence properties and cellular distribution of the investigational anticancer drug triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) and its zinc (II) complex. Dalton Transactions, 2010. 39(3): p. 704-706.
62. Qiao, M., J.D. Iglehart, and A.B. Pardee, Metastatic potential of 21T human breast cancer cells depends on Akt/protein kinase B activation. Cancer research, 2007. 67(11): p. 5293-5299.
63. Franke, T.F., S.-I. Yang, T.O. Chan, K. Datta, A. Kazlauskas, D.K. Morrison, D.R. Kaplan, and P.N. Tsichlis, The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell, 1995. 81(5): p. 727-736.
64. Calvo, E., V. Bolós, and E. Grande, Multiple roles and therapeutic implications of Akt signaling in cancer. OncoTargets and therapy, 2009. 2: p. 135.
65. Yoeli-Lerner, M. and A. Toker, Akt/PKB signaling in cancer: a function in cell motility and invasion. Cell cycle, 2006. 5(6): p. 603-605.
66. Qiao, M., S. Sheng, and A.B. Pardee, Metastasis and AKT activation. Cell cycle, 2008. 7(19): p. 2991-2996.
67. Poincloux, R., F. Lizárraga, and P. Chavrier, Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. J Cell Sci, 2009. 122(17): p. 3015-3024.
68. Gingras, D. and R. Béliveau, Emerging concepts in the regulation of membrane-type 1 matrix metalloproteinase activity. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2010. 1803(1): p. 142-150.
69. Egeblad, M. and Z. Werb, New functions for the matrix metalloproteinases in cancer progression. Nature Reviews Cancer, 2002. 2(3): p. 161-174.
70. Mazzone, M., M. Baldassarre, G. Beznoussenko, G. Giacchetti, J. Cao, S. Zucker, A. Luini, and R. Buccione, Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains. Journal of cell science, 2004. 117(26): p. 6275-6287.
71. Itoh, Y., A. Takamura, N. Ito, Y. Maru, H. Sato, N. Suenaga, T. Aoki, and M. Seiki, Homophilic complex formation of MT1‐MMP facilitates proMMP‐2 activation on the cell surface and promotes tumor cell invasion. The EMBO journal, 2001. 20(17): p. 4782-4793.
72. Morley, M., K. Riches, C. Peers, and K. Porter, Hypoxic inhibition of human cardiac fibroblast invasion and MMP-2 activation may impair adaptive myocardial remodelling. 2007, Portland Press Limited.
73. Overall, C.M. and R.A. Dean, Degradomics: systems biology of the protease web. Pleiotropic roles of MMPs in cancer. Cancer and Metastasis Reviews, 2006. 25(1): p. 69-75.
74. Deryugina, E.I. and J.P. Quigley, Matrix metalloproteinases and tumor metastasis. Cancer and Metastasis Reviews, 2006. 25(1): p. 9-34.
75. Hotary, K.B., E.D. Allen, P.C. Brooks, N.S. Datta, M.W. Long, and S.J. Weiss, Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell, 2003. 114(1): p. 33-45.
76. Hofmann, U.B., A.A. Eggert, K. Blass, E.-B. Bröcker, and J.C. Becker, Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer research, 2003. 63(23): p. 8221-8225.
77. Bowden, E.T., M. Barth, D. Thomas, R.I. Glazer, and S.C. Mueller, An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation. Oncogene, 1999. 18(31).
78. Buccione, R., J.D. Orth, and M.A. McNiven, Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nature reviews Molecular cell biology, 2004. 5(8): p. 647-658.
79. Kalinowska, M., G. Świderski, M. Matejczyk, and W. Lewandowski, Spectroscopic, thermogravimetric and biological studies of Na (I), Ni (II) and Zn (II) complexes of quercetin. Journal of Thermal Analysis and Calorimetry, 2016. 126(1): p. 141-148.
80. Azeez, L., A.O. Oyedeji, S.O. Adewuyi, and K.O. Tijani, Syntheses, characterizations and antioxidant activities of copper complexes of quercetin as influenced by redox states. International Journal of Biological and Chemical Sciences, 2015. 9(5): p. 2712-2718.
81. Zhai, G., W. Zhu, Y. Duan, W. Qu, and Z. Yan, Synthesis, characterization and antitumor activity of the germanium-quercetin complex. 2012.
82. Raza, A., X. Xu, L. Xia, C. Xia, J. Tang, and Z. Ouyang, Quercetin-iron complex: synthesis, characterization, antioxidant, DNA binding, DNA cleavage, and antibacterial activity studies. Journal of fluorescence, 2016. 26(6): p. 2023-2031.
83. Yang, S., B. Yin, L. Xu, B. Gao, H. Sun, L. Du, Y. Tang, W. Jiang, and F. Cao, A natural quercetin-based fluorescent sensor for highly sensitive and selective detection of copper ions. Analytical Methods, 2015. 7(11): p. 4546-4551.
84. De Souza, R.F. and W.F. De Giovani, Antioxidant properties of complexes of flavonoids with metal ions. Redox Report, 2004. 9(2): p. 97-104.
85. Tu, L.-Y., J. Pi, H. Jin, J.-Y. Cai, and S.-P. Deng, Synthesis, characterization and anticancer activity of kaempferol-zinc (II) complex. Bioorganic & medicinal chemistry letters, 2016. 26(11): p. 2730-2734.
86. Dehghan, G., J.E.N. Dolatabadi, A. Jouyban, K.A. Zeynali, S.M. Ahmadi, and S. Kashanian, Spectroscopic studies on the interaction of quercetin–terbium (III) complex with calf thymus DNA. DNA and cell biology, 2011. 30(3): p. 195-201.
87. Kontogianni, V.G., P. Charisiadis, A. Primikyri, C.G. Pappas, V. Exarchou, A.G. Tzakos, and I.P. Gerothanassis, Hydrogen bonding probes of phenol–OH groups. Organic & biomolecular chemistry, 2013. 11(6): p. 1013-1025.
88. Reedijk, J., New clues for platinum antitumor chemistry: kinetically controlled metal binding to DNA. Proceedings of the National Academy of Sciences, 2003. 100(7): p. 3611-3616.
89. Sathiyaraj, S., R.J. Butcher, and C. Jayabalakrishnan, Synthesis, characterization, DNA interaction and in vitro cytotoxicity activities of ruthenium (II) Schiff base complexes. Journal of Molecular Structure, 2012. 1030: p. 95-103.
90. Musumeci, D., L. Rozza, A. Merlino, L. Paduano, T. Marzo, L. Massai, L. Messori, and D. Montesarchio, Interaction of anticancer Ru (III) complexes with single stranded and duplex DNA model systems. Dalton Transactions, 2015. 44(31): p. 13914-13925.
91. Hecht, S.M., Bleomycin: new perspectives on the mechanism of action 1. Journal of natural products, 2000. 63(1): p. 158-168.
92. Metcalfe, C. and J.A. Thomas, Kinetically inert transition metal complexes that reversibly bind to DNA. Chemical Society Reviews, 2003. 32(4): p. 215-224.
93. Gurova, K., New hopes from old drugs: revisiting DNA-binding small molecules as anticancer agents. Future oncology, 2009. 5(10): p. 1685-1704.
94. Costello, L., P. Feng, B. Milon, M. Tan, and R. Franklin, Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve. Prostate cancer and prostatic diseases, 2004. 7(2): p. 111-117.
95. Hong, S.-H., Y.S. Choi, H.J. Cho, J.Y. Lee, T.-K. Hwang, and S.W. Kim, Induction of apoptosis of bladder cancer cells by zinc-citrate compound. Korean journal of urology, 2012. 53(11): p. 800-806.
96. Tanagornmeatar, K., C. Chaotham, B. Sritularak, K. Likhitwitayawuid, and P. Chanvorachote, Cytotoxic and anti-metastatic activities of phenolic compounds from Dendrobium ellipsophyllum. Anticancer research, 2014. 34(11): p. 6573-6579.
97. Weng, C.-J. and G.-C. Yen, Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer and Metastasis Reviews, 2012. 31(1-2): p. 323-351.
98. Sounni, N.E., L. Devy, A. Hajitou, F. Frankenne, C. Munaut, C. Gilles, C. Deroanne, E.W. Thompson, J.-M. Foidart, and A. Noël, MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression. The FASEB Journal, 2002. 16(6): p. 555-564.
99. Chun, T.-H., F. Sabeh, I. Ota, H. Murphy, K.T. McDonagh, K. Holmbeck, H. Birkedal-Hansen, E.D. Allen, and S.J. Weiss, MT1-MMP–dependent neovessel formation within the confines of the three-dimensional extracellular matrix. J Cell Biol, 2004. 167(4): p. 757-767.
100. Knäuper, V., H. Will, C. López-Otin, B. Smith, S.J. Atkinson, H. Stanton, R.M. Hembry, and G. Murphy, Cellular mechanisms for human procollagenase-3 (MMP-13) activation Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. Journal of Biological Chemistry, 1996. 271(29): p. 17124-17131.
101. Will, H., S.J. Atkinson, G.S. Butler, B. Smith, and G. Murphy, The soluble catalytic domain of membrane type 1 matrix metalloproteinase cleaves the propeptide of progelatinase A and initiates autoproteolytic activation Regulation by TIMP-2 and TIMP-3. Journal of Biological Chemistry, 1996. 271(29): p. 17119-17123.
102. Holopainen, J.M., J.A. Moilanen, T. Sorsa, M. Kivelä-Rajamäki, T. Tervahartiala, M.H. Vesaluoma, and T.M. Tervo, Activation of matrix metalloproteinase-8 by membrane type 1-MMP and their expression in human tears after photorefractive keratectomy. Investigative ophthalmology & visual science, 2003. 44(6): p. 2550-2556.
103. Gkouveris, I., Matrix metalloproteinases in head and neck cancer: current perspectives. 2017.
104. Selvaraj, S., S. Krishnaswamy, V. Devashya, S. Sethuraman, and U.M. Krishnan, Flavonoid–metal ion complexes: a novel class of therapeutic agents. Medicinal research reviews, 2014. 34(4): p. 677-702.
105. Cao, W., W. Zheng, and T. Chen, Ruthenium polypyridyl complex inhibits growth and metastasis of breast cancer cells by suppressing FAK signaling with enhancement of TRAIL-induced apoptosis. Scientific reports, 2015. 5: p. srep09157.
106. Lin, J.-J., J.-H. Su, C.-C. Tsai, Y.-J. Chen, M.-H. Liao, and Y.-J. Wu, 11-epi-Sinulariolide acetate reduces cell migration and invasion of human hepatocellular carcinoma by reducing the activation of ERK1/2, p38MAPK and FAK/PI3K/AKT/mTOR signaling pathways. Marine drugs, 2014. 12(9): p. 4783-4798.
107. Zhou, R., L. Xu, M. Ye, M. Liao, H. Du, and H. Chen, Formononetin inhibits migration and invasion of MDA-MB-231 and 4T1 breast cancer cells by suppressing MMP-2 and MMP-9 through PI3K/AKT signaling pathways. Hormone and metabolic research, 2014. 46(11): p. 753-760.
108. Ko, H.S., H.-J. Lee, S.-H. Kim, and E.-O. Lee, Piceatannol suppresses breast cancer cell invasion through the inhibition of MMP-9: involvement of PI3K/AKT and NF-κB pathways. Journal of agricultural and food chemistry, 2012. 60(16): p. 4083-4089.
109. LU, C.-C., J.-S. Yang, J.-H. Chiang, M.-J. Hour, S. Amagaya, K.-W. Lu, J.-P. Lin, N.-Y. Tang, T.-H. Lee, and J.-G. Chung, Inhibition of invasion and migration by newly synthesized quinazolinone MJ-29 in human oral cancer CAL 27 cells through suppression of MMP-2/9 expression and combined down-regulation of MAPK and AKT signaling. Anticancer research, 2012. 32(7): p. 2895-2903.
110. Oudart, J.-B., M. Doué, A. Vautrin, B. Brassart, C. Sellier, A. Dupont-Deshorgue, J.-C. Monboisse, F.-X. Maquart, S. Brassart-Pasco, and L. Ramont, The anti-tumor NC1 domain of collagen XIX inhibits the FAK/PI3K/Akt/mTOR signaling pathway through αvβ3 integrin interaction. Oncotarget, 2016. 7(2): p. 1516.
111. Sun, X., X. Wang, T. Chen, T. Li, K. Cao, A. Lu, Y. Chen, D. Sun, J. Luo, and J. Fan, Myelin activates FAK/Akt/NF-κB pathways and provokes CR3-dependent inflammatory response in murine system. PLoS One, 2010. 5(2): p. e9380.
112. Furuya, F., J.A. Hanover, and S.-y. Cheng, Activation of phosphatidylinositol 3-kinase signaling by a mutant thyroid hormone β receptor. Proceedings of the National Academy of Sciences of the United States of America, 2006. 103(6): p. 1780-1785.
113. Zhou, H.Y. and A.S. Wong, Activation of p70S6K induces expression of matrix metalloproteinase 9 associated with hepatocyte growth factor-mediated invasion in human ovarian cancer cells. Endocrinology, 2006. 147(5): p. 2557-2566.
114. Lee, E.J., D.I. Kim, W.J. Kim, and S.K. Moon, Naringin inhibits matrix metalloproteinase‐9 expression and AKT phosphorylation in tumor necrosis factor‐α‐induced vascular smooth muscle cells. Molecular nutrition & food research, 2009. 53(12): p. 1582-1591.
115. Gong, Y., U.D. Chippada-Venkata, and W.K. Oh, Roles of matrix metalloproteinases and their natural inhibitors in prostate cancer progression. Cancers, 2014. 6(3): p. 1298-1327.
116. Su, Q., M. Peng, Y. Zhang, W. Xu, K.O. Darko, T. Tao, Y. Huang, X. Tao, and X. Yang, Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway. American journal of cancer research, 2016. 6(2): p. 498
指導教授 李宇翔(Yu-Hsiang Lee) 審核日期 2018-1-23
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題,請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407,或E-mail聯絡  - 隱私權政策聲明