Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 生化科技學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55969
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor何佳安
dc.contributor.authorJie-Fu Chenen
dc.contributor.author陳介甫zh_TW
dc.date.accessioned2021-06-16T05:11:56Z-
dc.date.available2024-08-19
dc.date.copyright2014-08-22
dc.date.issued2014
dc.date.submitted2014-08-19
dc.identifier.citation1. 林青榖、趙瑞芹, 粗食,身體也需要斷捨離. 2012/10/11.
2. Hanahan, D. and Robert A. Weinberg, Hallmarks of Cancer: The Next
Generation. Cell. 144(5): p. 646-674.
3. McNeal, J.E., et al., Zonal Distribution of Prostatic Adenocarcinoma:
Correlation with Histologic Pattern and Direction of Spread. The
American Journal of Surgical Pathology, 1988. 12(12): p. 897-906.
4. Hsing, A.W., L. Tsao, and S.S. Devesa, International trends and patterns of prostate cancer incidence and mortality. International Journal of
Cancer, 2000. 85(1): p. 60-67.
5. Haenszel, W. and M. Kurihara, Studies of Japanese migrants. I.
Mortality from cancer and other diseases among Japanese in the United
States. J Natl Cancer Inst, 1968. 40(1): p. 43-68.
6. Mettlin, C., et al., Defining and updating the american cancer society
guidelines for the cancer-related checkup: Prostate and endometrial
cancers. CA: A Cancer Journal for Clinicians, 1993. 43(1): p. 42-46.
7. American Urological Association: Early detection of prostate cancer and the use of transrectal ultrasound. A. U. A. policy statement book,
1992. 4:20.
8. Gann, P.H., C.H. Hennekens, and M.J. Stampfer, A prospective
evaluation of plasma prostate-specific antigen for detection of
prostatic cancer. JAMA, 1995. 273(4): p. 289-294.
9. Wu, H.-C., et al., Derivation of androgen-independent human LNCaP
prostatic cancer cell sublines: Role of bone stromal cells. International
Journal of Cancer, 1994. 57(3): p. 406-412.
10. Gleason, D.F., Classification of prostatic carcinomas. Cancer
Chemother Rep, 1966. 50(3): p. 125-8.
11. Tascilar, M., et al., Complementary and alternative medicine during
cancer treatment: beyond innocence. Oncologist, 2006. 11(7): p.
732-41.
12. Xie, W., et al., Botany, traditional uses, phytochemistry and
pharmacology of Apocynum venetum L. (Luobuma): A review. J
Ethnopharmacol, 2012. 141(1): p. 1-8.
13. 方學良, 塔里木盆地大葉白麻土壤生長環境類型. 植物生態學與植物學學報, 1986. 10(1):: p. 52-48.
14. 中國科學院植物志編委會. 中國志, 1977. 第 63 卷 : p. 87.
15. Kim, D.W., et al., Inhibitory effects of an aqueous extract of Apocynum
venetum leaves and its constituents on Cu(2+)-induced oxidative modification of low density lipoprotein. Phytother Res, 2000. 14(7): p. 501-4.
16. Kamata, K., S. Seo, and J. Nakajima, Constituents from leaves of Apocynum venetum L. J Nat Med, 2008. 62(2): p. 160-3.
17. Yokozawa, T. and T. Nakagawa, Inhibitory effects of Luobuma tea and its components against glucose-mediated protein damage. Food Chem Toxicol, 2004. 42(6): p. 975-81.
18. Yokozawa, T., et al., Magnesium lithospermate B suppresses the increase of active oxygen in rats after subtotal nephrectomy. Nephron, 1997. 75(1): p. 88-93.
19. Shirai, M., et al., Approach to novel functional foods for stress control 5. Antioxidant activity profiles of antidepressant herbs and their active components. J Med Invest, 2005. 52 Suppl: p. 249-51.
20. Xiong, Q., et al., Hepatoprotective effect of Apocynum venetum and its active constituents. Planta Med, 2000. 66(2): p. 127-33.
21. Kim, D., et al., Effects of aqueous extracts of Apocynum venetum leaves
on spontaneously hypertensive, renal hypertensive and NaCl-fed-hypertensive rats. J Ethnopharmacol, 2000. 72(1-2): p. 53-9.
22. Grundmann, O., et al., Anti-anxiety effects of Apocynum venetum L. in the elevated plus maze test. J Ethnopharmacol, 2007. 110(3): p. 406-11.
23. Butterweck, V., et al., Antidepressant effects of apocynum venetum leaves in a forced swimming test. Biol Pharm Bull, 2001. 24(7): p. 848-51.
24. Grundmann, O., et al., Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice. Phytomedicine, 2009. 16(4): p. 295-302.
25. Song, G., et al., Effects of oxymatrine on proliferation and apoptosis in human hepatoma cells. Colloids Surf B Biointerfaces, 2006. 48(1): p. 1-5.
26. Waterman, E. and B. Lockwood, Active components and clinical applications of olive oil. Altern Med Rev, 2007. 12(4): p. 331-42.
27. Beveridge, T.H., T.S. Li, and J.C. Drover, Phytosterol content in
American ginseng seed oil. J Agric Food Chem, 2002. 50(4): p. 744-50.
28. Hata, K., et al., Differentiation-inducing activity of lupeol, a lupane-type triterpene from Chinese dandelion root (Hokouei-kon), on
a mouse melanoma cell line. Biol Pharm Bull, 2000. 23(8): p. 962-7.
29. Hata, K., K. Hori, and S. Takahashi, Role of p38 MAPK in lupeol-induced
B16 2F2 mouse melanoma cell differentiation. J Biochem, 2003. 134(3):
p. 441-5.
30. Hata, K., et al., Remodeling of actin cytoskeleton in lupeol-induced B16
2F2 cell differentiation. J Biochem, 2005. 138(4): p. 467-72.
31. Saleem, M., Lupeol, a novel anti-inflammatory and anti-cancer dietary
triterpene. Cancer Lett, 2009. 285(2): p. 109-15.
32. Lambertini, E., et al., Expression of estrogen receptor alpha gene in
breast cancer cells treated with transcription factor decoy is modulated by Bangladeshi natural plant extracts. Oncol Res, 2005. 15(2): p. 69-79.
33. Saleem, M., et al., Lupeol modulates NF-kappaB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice. Oncogene, 2004. 23(30): p. 5203-14.
34. Saleem, M., et al., Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway. Carcinogenesis, 2005. 26(11): p. 1956-64.
35. Murtaza, I., et al., Suppression of cFLIP by lupeol, a dietary triterpene, is sufficient to overcome resistance to TRAIL-mediated apoptosis in chemoresistant human pancreatic cancer cells. Cancer Res, 2009. 69(3): p. 1156-65.
36. Prasad, S., et al., Regulation of signaling pathways involved in lupeol induced inhibition of proliferation and induction of apoptosis in human prostate cancer cells. Mol Carcinog, 2008. 47(12): p. 916-24.
37. Siddique, H.R., et al., Lupeol, a novel androgen receptor inhibitor: implications in prostate cancer therapy. Clin Cancer Res, 2011. 17(16): p. 5379-91.
38. Saleem, M., et al., Lupeol inhibits proliferation of human prostate cancer cells by targeting beta-catenin signaling. Carcinogenesis, 2009.
30(5): p. 808-17.
39. Prasad, S., et al., Protective effects of lupeol and mango extract against
androgen induced oxidative stress in Swiss albino mice. Asian J Androl,
2008. 10(2): p. 313-8.
40. Pardee, A.B., G1 events and regulation of cell proliferation. Science,
1989. 246(4930): p. 603-8.
41. Hsing, A.W., Hormones and prostate cancer: what's next? Epidemiol
Rev, 2001. 23(1): p. 42-58.
42. Brown, J.R., et al., Fos family members induce cell cycle entry by
activating cyclin D1. Mol Cell Biol, 1998. 18(9): p. 5609-19.
43. Wu, L. and A.J. Levine, Differential regulation of the p21/WAF-1 and mdm2 genes after high-dose UV irradiation: p53-dependent and p53-independent regulation of the mdm2 gene. Mol Med, 1997. 3(7): p.
441-51.
44. Chen, Y.N., et al., Selective killing of transformed cells by
cyclin/cyclin-dependent kinase 2 antagonists. Proc Natl Acad Sci U S A,
1999. 96(8): p. 4325-9.
45. Krek, W., G. Xu, and D.M. Livingston, Cyclin A-kinase regulation of
E2F-1 DNA binding function underlies suppression of an S phase
checkpoint. Cell, 1995. 83(7): p. 1149-58.
46. Weinert, T., A DNA damage checkpoint meets the cell cycle engine.
Science, 1997. 277(5331): p. 1450-1.
47. Bunz, F., et al., Requirement for p53 and p21 to sustain G2 arrest after
DNA damage. Science, 1998. 282(5393): p. 1497-501.
48. Hetts, S.W., To die or not to die: an overview of apoptosis and its role in
disease. Jama, 1998. 279(4): p. 300-7.
49. Gozuacik, D. and A. Kimchi, Autophagy as a cell death and tumor
suppressor mechanism. Oncogene, 2004. 23(16): p. 2891-906.
50. Coucouvanis, E. and G.R. Martin, Signals for death and survival: a
two-step mechanism for cavitation in the vertebrate embryo. Cell, 1995.
83(2): p. 279-87.
51. Bursch, W., et al., Programmed cell death (PCD). Apoptosis, autophagic
PCD, or others? Ann N Y Acad Sci, 2000. 926: p. 1-12.
52. Wyllie, A.H., Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature, 1980. 284(5756): p.
555-6.
53. Widlak, P., The DFF40/CAD endonuclease and its role in apoptosis. Acta
Biochim Pol, 2000. 47(4): p. 1037-44.
54. Wyllie, A.H., Apoptosis and carcinogenesis. Eur J Cell Biol, 1997. 73(3):
p. 189-97.
55. Wyllie, A.H., Apoptosis: an overview. Br Med Bull, 1997. 53(3): p.
451-65.
56. Hiramine, C., [Definition and morphological features of apoptosis].
Rinsho Byori, 1997. 45(5): p. 459-69.
57. Link, C.J., et al., Cellular suicide therapy of malignant disease. Stem
Cells, 2000. 18(3): p. 220-6.
58. Smith, C.A., T. Farrah, and R.G. Goodwin, The TNF receptor superfamily
of cellular and viral proteins: activation, costimulation, and death. Cell,
1994. 76(6): p. 959-62.
59. Sessler, T., et al., Structural determinants of DISC function: new
insights into death receptor-mediated apoptosis signalling. Pharmacol
Ther, 2013. 140(2): p. 186-99.
60. Fulda, S., Caspase-8 in cancer biology and therapy. Cancer Lett, 2009.
281(2): p. 128-33.
61. Zhao, Y., X. Sui, and H. Ren, From procaspase-8 to caspase-8: revisiting
structural functions of caspase-8. J Cell Physiol, 2010. 225(2): p.
316-20.
62. Ulivieri, C., Cell death: insights into the ultrastructure of mitochondria.
Tissue Cell, 2010. 42(6): p. 339-47.
63. Riedl, S.J. and Y. Shi, Molecular mechanisms of caspase regulation
during apoptosis. Nat Rev Mol Cell Biol, 2004. 5(11): p. 897-907.
64. Thornberry, N.A. and Y. Lazebnik, Caspases: enemies within. Science,
1998. 281(5381): p. 1312-6.
65. Kang, Y.H., et al., Caspase-independent cell death by arsenic trioxide in
human cervical cancer cells: reactive oxygen species-mediated poly(ADP-ribose) polymerase-1 activation signals apoptosis-inducing factor release from mitochondria. Cancer Res, 2004. 64(24): p. 8960-7.
66. Nagata, S., Apoptotic DNA Fragmentation. Experimental Cell Research,2000. 256(1): p. 12-18.
67. Saraste, A. and K. Pulkki, Morphologic and biochemical hallmarks of
apoptosis. Cardiovasc Res, 2000. 45(3): p. 528-37.
68. Goping, I.S., et al., Regulated targeting of BAX to mitochondria. J Cell
Biol, 1998. 143(1): p. 207-15.
69. Green, D.R. and J.C. Reed, Mitochondria and apoptosis. Science, 1998.
281(5381): p. 1309-12.
70. Korsmeyer, S.J., et al., Bcl-2/Bax: a rheostat that regulates an
anti-oxidant pathway and cell death. Semin Cancer Biol, 1993. 4(6): p.
327-32.
71. 莊安卓, 奇蹟之飲-羅布麻的神奇功效. 2006: 元氣齋.
72. Peng, C.H., et al., Penta-acetyl geniposide induce apoptosis in C6 glioma
cells by modulating the activation of neutral sphingomyelinase-induced p75 nerve growth factor receptor and protein kinase Cdelta pathway. Mol Pharmacol, 2006. 70(3): p. 997-1004.
73. Blois, S., A note on free radical formation in biologically occurring quinones. Biochim Biophys Acta, 1955. 18(1): p. 165.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55969-
dc.description.abstract前列腺癌不管在西方或東方的癌症死亡率都有逐年增高的趨勢;根據 2013 年台灣衛生福利部國民健康署統計,前列腺癌佔國人主要癌症死亡排名 第七名;American Cancer Society 則指出前列腺癌佔美國男性死亡排名第二 名。因此如何有效防治前列腺癌是目前醫學研究人員極欲深入了解的議題。 相關文獻及資料持續提到中草藥對於抗癌的成效,過去的研究也證實中草藥 中萃取出的多酚與黃酮類物質具有抗癌的效果。本研究以一系列羅布麻萃取 物為主,探討其抑制惡性前列腺癌細胞株 PC3 生長及增生的潛力。細胞毒殺 試驗(MTT assay)測試結果發現,編號 8 萃取物有最好的抑制癌細胞生長 的效果(IC50:172 μg/mL,24h)。以流式細胞儀(flow cytometry)分析之 結果發現羅布麻 8 號的萃取物會造成細胞週期 G2/M 停滯(G2/M arrest)及 細胞凋亡(apoptosis)的現象,且此現象呈現劑量依賴性(dose-dependent)。 化學分析實驗發現羅布麻萃取物內含有大量酚類(phenol)、黃酮類 (flavonoid),同時發現其有很強的抗氧化。經過核磁共振光譜儀及質譜儀 進行結構鑑定和分析,可以得知有效抑制癌細胞生長/增生的羅布麻萃取物中 的有效主成分是羽扇豆醇(Lupeol)。因此,我們利用市售羽扇豆醇標準品再 次進行上述細胞試驗。結果發現其抑制癌細胞生長/增生的效果及特性與編號 8 羅布麻萃取物相似(IC50:23 μg/mL,24h);相同的,流式細胞儀分析和 DAPI 染色法也觀察到癌細胞 G2/M 停滯的現象。總結研究成果,本論文發 現,編號 8 羅布麻萃取物對於開發成前列腺癌治療的藥物或保健食品具有相 當的潛力。zh_TW
dc.description.abstractMalignancy is most aware as a description of cancer, which is difficult to cure. Surgery is referred to as the oldest procedure in treating cancer, about 60 -70% of cancer patients will undergo surgery, either by itself or in combination with other therapies, such as chemotherapy. Prostate cancer is an age-related cancer, ranking as the seventh leading cause of cancer death among men in Taiwan, and the second in the United States. Several traditional herbal medicines have been found to have antitumor effects, previous studies indicated that numerous Chinese herbal medicines not only demonstrated anti-inflammatory, anti-oxidative and anti-tumor effect, but also exerted low toxic side effects. In this study, the possible cytotoxic or growth-inhibitory effect of the Apocynum venetum (Luobuma) extracts was investigated. MTT assays were performed and found out the #8 fraction of the Apocynum venetum extracts possessed the greatest ability in halting the growth/proliferation of the prostate cancer (PC3). Further, flow cytometric analysis were conduct to confirm the effects of Apocynum venetum extracts in inducing apoptosis in PC3, and it was found that Apocynum venetum extract #8 was able to increase the G2/M phase ratio during cell cycle progression. Moreover nuclear condensation was also confirmed by DAPI staining in PC3 cells. Further the total phenolic and total flavonoids contents were measured. The anti-oxidant ability of the Apocynum venetum extracts #8 was also determined by ABTS+, DPPH and FRASC assay, respectively. NMR and Mass spectrometric analyses confirmed the most abundant compound presented in Apocynum venetum extract fraction#8 is lupeol.Commercial lupeol standard was purchased to test its anti-proliferation effect on PC-3 cancer cells, similar results was observed. Based on the collective observations, it was thus concluded that Apocynum venetum extract containing lupeol plays an important role in activating/mediating apoptosis, and G2/M phase arrest in PC3 prostate cancer cells. Apocynum venetum may hold the great promise as one effective compound for treating prostate cancer or becoming a functional food ingredient to reduce risk of prostate cancer.en
dc.description.provenanceMade available in DSpace on 2021-06-16T05:11:56Z (GMT). No. of bitstreams: 1
ntu-103-R01b22041-1.pdf: 6515029 bytes, checksum: 3ce0979c2be888cc5540556ca22fa7eb (MD5)
Previous issue date: 2014
en
dc.description.tableofcontents目錄
中文摘要......................................................................................I
英文摘要.....................................................................................II
圖表目錄....................................................................................IV
壹、文獻回顧...............................................................................1
一、概述.....................................................................................1
二、惡性腫瘤...............................................................................1
(一)惡性腫瘤簡介.........................................................................1
(二)惡性腫瘤特徵.........................................................................2
三、前列腺及前列腺癌...................................................................4
(一)前列腺簡介............................................................................4
(二)良性前列腺肥大......................................................................5
(三)前列腺癌................................................................................6
(四)前列腺癌目前之現狀................................................................6
(五)前列腺癌之診斷及治療.............................................................7
四、羅布麻.................................................................................10
(一)補充與另類醫療(CAM)...........................................................10
(二)羅布麻簡介...........................................................................11
(三)羅布麻之社會經濟價值...........................................................12
(四)羅布麻之藥用功效.................................................................13
五、羽扇豆醇(Lupeol).................................................................14
六、細胞週期.............................................................................16
(一)G0/G1 phase......................................................................16
(二)S phase..............................................................................16
(三)G2 phase............................................................................17
七、細胞凋亡.............................................................................18
(一)定義....................................................................................18
(二)第一型程序性細胞死亡...........................................................19
(三)細胞凋亡之分子機轉..............................................................20
貳、研究動機..............................................................................26
參、研究架構........................................................,.....................27
肆、實驗藥品與器材....................................................................28
伍、實驗方法..............................................................................31
一、天然物分析...........................................................................31
(一)羅布麻萃取物類黃酮含量測定..................................................31
(二)羅布麻萃取物總酚含量測定.....................................................32
(三)羅布麻萃取物以 DPPH 測定法測定其抗氧化能力........................32
(四)羅布麻萃取物以 ABTS•+ 測定法測定其抗氧化能力.....................33
二、細胞實驗..............................................................................35
(一)細胞培養..............................................................................35
(二)細胞冷凍及解凍.....................................................................36
(三)細胞毒性測試........................................................................36
(四)流式細胞儀技術分析細胞週期..................................................37
(五)DAPI 染色法.........................................................................39
(六)AVO 染色法..........................................................................40
(七)蛋白質萃取及定量..................................................................41
(八)西方墨點法...........................................................................44
(九)活性氧物質偵測.....................................................................47
陸、實驗結果..............................................................................49
一、羅布麻萃取物對前列腺癌細胞之毒性測試.................................49
二、羅布麻萃取物之總酚和類黃酮含量測定....................................53
三、羅布麻萃取物之抗氧化能力測定..............................................55
四、羅布麻萃取物對前列腺癌細胞之細胞週期影響...........................56
五、羽扇豆醇對前列腺癌細胞之毒性測試........................................60
六、羽扇豆醇對前列腺癌細胞之細胞週期影響..................................61
柒、討論......................................................................................65
捌、參考文獻...............................................................................68
dc.language.isozh-TW
dc.subject羅布麻zh_TW
dc.subject前列腺癌zh_TW
dc.subject抗癌zh_TW
dc.subjectprostate canceren
dc.subjectanti-canceren
dc.subjectApocynum venetumen
dc.title羅布麻萃取物在人類前列腺癌細胞株的抗癌作用zh_TW
dc.titleThe anti-cancer effect of Apocynum venetum extract in a prostate cancer cell lineen
dc.typeThesis
dc.date.schoolyear102-2
dc.description.degree碩士
dc.contributor.coadvisor蕭寧馨
dc.contributor.oralexamcommittee徐士蘭,蘇純立,吳立真
dc.subject.keyword羅布麻,前列腺癌,抗癌,zh_TW
dc.subject.keywordanti-cancer,Apocynum venetum,prostate cancer,en
dc.relation.page73
dc.rights.note有償授權
dc.date.accepted2014-08-19
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept生化科技學系zh_TW
顯示於系所單位:生化科技學系

文件中的檔案:
檔案 大小格式 
ntu-103-1.pdf
  未授權公開取用
6.36 MBAdobe PDF
顯示文件簡單紀錄


系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved