薑黃素衍生物ASC-J9對MDA-MB-231人類三陰性乳腺癌細胞生長和轉移之影響

Effect of curcumin analog ASC-J9 on cell survival and metastasis in MDA-MB-231 triple-negative human breast cancer cell

王鈺翔

ASC-J9 ； 基質金屬蛋白酶-9 ； 轉移 ； 凋亡 ； 壞死 ； MDA-MB-231乳癌細胞 ； ASC-J9 ； Matrix metalloproteinase-9 ； Metastasis ； Apoptosis ； Necrosis ； MDA-MB-231 breast cancer cell

中山醫學大學營養學研究所學位論文

2016年

碩士

李健群

繁體中文

根據衛生福利部民國103年十大癌症死亡統計，女性乳房腫瘤排名第四，相較於其它歐美國家，國內的乳癌女性患者有年輕化趨勢，因此對於如何降低乳癌的發生和致死率，為目前重要研究課題。ASC-J9為薑黃素(curcumin)的衍生物之一，少數研究證實它對前列腺癌具有抑制效果，然而ASC-J9是否對於乳癌具有抗癌效果仍未知。本研究利用細胞和動物模式，探討ASC-J9對高惡性度MDA-MB-231三陰性乳癌細胞株生長、轉移之影響。結果顯示：處理0.1、0.5、1、5 μM ASC-J9 24小時後可顯著抑制MMP-9酵素活性、蛋白質和mRNA表現量並抑制乳癌細胞移行(migration)和侵襲(invasion)。處理ASC-J960分鐘後可顯著抑制JNK和p38磷酸化，若以JNK和p38抑制劑處理細胞亦可降低MMP-9蛋白質表現。以ASC-J9處理MDA-MB-231細胞120分鐘後，可顯著抑制c-jun核蛋白表現量並透過electrophoretic mobility shift assay方法證實ASC-J9可降低c-jun和AP-1 binding site的結合能力。由細胞存活率分析及凋亡檢測實驗結果得知，處理高劑量ASC-J9 (10、20、30 μM ) 24小時後，可改變Bax/Bcl-2的比例並誘發MDA-MB-231細胞caspase 3、PARP蛋白質表現量並促使乳癌細胞壞死(Necrosis )、凋亡(Apoptosis )。由上述結果證明低劑量ASC-J9可透過抑制JNK/p38訊號路徑降低c-jun核內蛋白質累積，進而減少其與AP-1結合能力，抑制MMP-9表現和活性，最終抑制乳癌細胞移行與侵襲。而高劑量ASC-J9則可誘發癌細胞壞死及凋亡。另外以帶有標記冷光酵素(luciferase)的MDA-MB-231三陰性乳癌細胞異體移植免疫缺陷小鼠(C.B17/Icr-Prkdcscid/CrlNarl mouse)為動物模式，餵食ASC-J9 (50 mg/kg)四週後能有效抑制腫瘤生長。綜合上述實驗結果ASC-J9具有抗乳癌細胞發展之潛力。

Breast cancer is the most prevalent cancer among women worldwide, and it was becoming more common in younger women. Reduction of incidence and death rate is still an important issue in the world. ASC-J9, an analog of curcumin, has been recognized as a potential antioxidant, demonstrated to have anti-cancer effect against human prostate cancer. However, this anti-cancer effect on human breast cancer is not fully clarified. In this study, we investigated the effect of ASC-J9 on cell growth and metastasis on MDA-MB-231 human triple-negative breast cancer cells. Results indicated that ASC-J9 dose-dependently inhibited MMP-9 protein, mRNA expression and enzyme activityas well as cell migration and invasion. The phosphorylation of JNK and P38 were suppressed by ASC-J9 treatment for 60 min. The MMP-9 protein expression were significantly inhibited by specific inhibitors of JNK and p38. Moreover, the nuclear accumulation of c-Jun protein and AP-1 DNA binding activitywere decreased by ASC-J9 treatment for 120 min. Treatment with high concentration of ASC-J9 (10, 20, 30 μM ) were able to change the ratio of Bax/Bcl-2 and induce caspase 3as well as PARP expression and activity, resulted in necrotistic and apoptotic cell death. The MDA-MB-231 breast cancer xenograftmodel in C.B17/ Icr-Prkdcscid/ CrlNarl mouse was used to exam the effect of ASC-J9 on tumor growth. Oral administration of ASC-J9 for four weeks suppressed tumor tumor growth. Taken together, our finding suggests that ASC-J9 has anti-tumor potentials against breast cancer development.

1. 行政院衛生署國健康局(2014):中華民國103癌症登記報告。台北:行政
   連結：
2. 院衛生署國民健康局編印
   連結：
3. 行政院衛生署(2014):中華民國103年死因統計結果分析。台北:行政院
   連結：
4. 衛生署國民健康局編印
   連結：
5. Abo-Salem, O. M., G. I. Harisa, T. M. Ali, S. M. El-Sayed el, and F. M. Abou-Elnour. 2014. 'Curcumin ameliorates streptozotocin-induced heart injury in rats', J Biochem Mol Toxicol, 28: 263-70.
   連結：
6. Altenburg, J. D., A. A. Bieberich, C. Terry, K. A. Harvey, J. F. Vanhorn, Z. Xu, V. Jo Davisson, and R. A. Siddiqui. 2011. 'A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone', BMC Cancer, 11: 149.
   連結：
7. Ame, J. C., C. Spenlehauer, and G. de Murcia. 2004. 'The PARP superfamily', Bioessays, 26: 882-93.
   連結：
8. Armstrong, J. S. 2006. 'Mitochondrial membrane permeabilization: the sine qua non for cell death', Bioessays, 28: 253-60.
   連結：
9. Baliga, B. C., and S. Kumar. 2002. 'Role of Bcl-2 family of proteins in malignancy', Hematol Oncol, 20: 63-74.
   連結：
10. Becker, C., A. J. Watson, and M. F. Neurath. 2013. 'Complex roles of caspases in the pathogenesis of inflammatory bowel disease', Gastroenterology, 144: 283-93.
    連結：
11. Bedal, K. B., S. Grassel, P. J. Oefner, J. Reinders, T. E. Reichert, and R. Bauer. 2014. 'Collagen XVI induces expression of MMP9 via modulation of AP-1 transcription factors and facilitates invasion of oral squamous cell carcinoma', PLoS One, 9: e86777.
    連結：
12. Bergers, G., R. Brekken, G. McMahon, T. H. Vu, T. Itoh, K. Tamaki, K. Tanzawa, P. Thorpe, S. Itohara, Z. Werb, and D. Hanahan. 2000. 'Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis', Nat Cell Biol, 2: 737-44.
    連結：
13. Bianchini, G., J. M. Balko, I. A. Mayer, M. E. Sanders, and L. Gianni. 2016. 'Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease', Nat Rev Clin Oncol.
    連結：
14. Boorjian, S., S. Ugras, N. P. Mongan, L. J. Gudas, X. You, S. K. Tickoo, and D. S. Scherr. 2004. 'Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer', Urology, 64: 383-8.
    連結：
15. Brenner, D., and T. W. Mak. 2009. 'Mitochondrial cell death effectors', Curr Opin Cell Biol, 21: 871-7.
    連結：
16. Certo, M., V. Del Gaizo Moore, M. Nishino, G. Wei, S. Korsmeyer, S. A. Armstrong, and A. Letai. 2006. 'Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members', Cancer Cell, 9: 351-65.
    連結：
17. Cetin, Idil, and Mehmet Topcul. 2014. 'Triple Negative Breast Cancer', Asian Pacific Journal of Cancer Prevention, 15: 2427-31.
    連結：
18. Chacon, R. D., and M. V. Costanzo. 2010. 'Triple-negative breast cancer', Breast Cancer Res, 12 Suppl 2: S3.
    連結：
19. Chen, H. W., C. Y. Chao, L. L. Lin, C. Y. Lu, K. L. Liu, C. K. Lii, and C. C. Li. 2013. 'Inhibition of matrix metalloproteinase-9 expression by docosahexaenoic acid mediated by heme oxygenase 1 in 12-O-tetradecanoylphorbol-13-acetate-induced MCF-7 human breast cancer cells', Arch Toxicol, 87: 857-69.
    連結：
20. Chen, L., S. N. Willis, A. Wei, B. J. Smith, J. I. Fletcher, M. G. Hinds, P. M. Colman, C. L. Day, J. M. Adams, and D. C. Huang. 2005. 'Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function', Mol Cell, 17: 393-403.
    連結：
21. Cheng, C., J. T. Jiao, Y. Qian, X. Y. Guo, J. Huang, M. C. Dai, L. Zhang, X. P. Ding, D. Zong, and J. F. Shao. 2016. 'Curcumin induces G2/M arrest and triggers apoptosis via FoxO1 signaling in U87 human glioma cells', Mol Med Rep, 13: 3763-70.
    連結：
22. Daniel, P. T., K. Schulze-Osthoff, C. Belka, and D. Guner. 2003. 'Guardians of cell death: the Bcl-2 family proteins', Essays Biochem, 39: 73-88.
    連結：
23. Festjens, N., T. Vanden Berghe, and P. Vandenabeele. 2006. 'Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response', Biochim Biophys Acta, 1757: 1371-87.
    連結：
24. Fidler, I. J. 2003. 'The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited', Nat Rev Cancer, 3: 453-8.
    連結：
25. Filipovic, D. M., X. Meng, and W. B. Reeves. 1999. 'Inhibition of PARP prevents oxidant-induced necrosis but not apoptosis in LLC-PK1 cells', Am J Physiol, 277: F428-36.
    連結：
26. Gialeli, C., A. D. Theocharis, and N. K. Karamanos. 2011. 'Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting', FEBS J, 278: 16-27.
    連結：
27. Goldar, S., M. S. Khaniani, S. M. Derakhshan, and B. Baradaran. 2015. 'Molecular mechanisms of apoptosis and roles in cancer development and treatment', Asian Pac J Cancer Prev, 16: 2129-44.
    連結：
28. Golstein, P., and G. Kroemer. 2007. 'Cell death by necrosis: towards a molecular definition', Trends Biochem Sci, 32: 37-43.
    連結：
29. Gunther, C., H. Neumann, M. F. Neurath, and C. Becker. 2013. 'Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium', Gut, 62: 1062-71.
    連結：
30. Gupta, G. P., and J. Massague. 2006. 'Cancer metastasis: building a framework', Cell, 127: 679-95.
    連結：
31. Hanahan, D., and R. A. Weinberg. 2000. 'The hallmarks of cancer', Cell, 100: 57-70.
    連結：
32. Hassan, M., H. Watari, A. AbuAlmaaty, Y. Ohba, and N. Sakuragi. 2014. 'Apoptosis and molecular targeting therapy in cancer', Biomed Res Int, 2014: 150845.
    連結：
33. He, D., L. Li, G. Zhu, L. Liang, Z. Guan, L. Chang, Y. Chen, S. Yeh, and C. Chang. 2014. 'ASC-J9 suppresses renal cell carcinoma progression by targeting an androgen receptor-dependent HIF2alpha/VEGF signaling pathway', Cancer Res, 74: 4420-30.
    連結：
34. Hegedus, C., and L. Virag. 2014. 'Inputs and outputs of poly(ADP-ribosyl)ation: Relevance to oxidative stress', Redox Biol, 2c: 978-82.
    連結：
35. Heinlein, C. A., and C. Chang. 2004. 'Androgen receptor in prostate cancer', Endocr Rev, 25: 276-308.
    連結：
36. Hengartner, M. O. 2000. 'The biochemistry of apoptosis', Nature, 407: 770-6.
    連結：
37. Henrotin, Y., M. Gharbi, Y. Dierckxsens, F. Priem, M. Marty, L. Seidel, A. Albert, E. Heuse, V. Bonnet, and C. Castermans. 2014. 'Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial', BMC Complement Altern Med, 14: 159.
    連結：
38. Henrotin, Y., F. Priem, and A. Mobasheri. 2013. 'Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management', Springerplus, 2: 56.
    連結：
39. Huang, D. C., J. M. Adams, and S. Cory. 1998. 'The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4', Embo j, 17: 1029-39.
    連結：
40. Huang, Q., F. Lan, X. Wang, Y. Yu, X. Ouyang, F. Zheng, J. Han, Y. Lin, Y. Xie, F. Xie, W. Liu, X. Yang, H. Wang, L. Dong, L. Wang, and J. Tan. 2014. 'IL-1beta-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9', Mol Cancer, 13: 18.
    連結：
41. Huang, Y. T., Y. W. Lin, H. M. Chiu, and B. H. Chiang. 2016. 'Curcumin Induces Apoptosis of Colorectal Cancer Stem Cells by Coupling with CD44 Marker', J Agric Food Chem, 64: 2247-53.
    連結：
42. Indran, I. R., G. Tufo, S. Pervaiz, and C. Brenner. 2011. 'Recent advances in apoptosis, mitochondria and drug resistance in cancer cells', Biochim Biophys Acta, 1807: 735-45.
    連結：
43. Jha, Niki S., Satyendra Mishra, Shailendra K. Jha, and Avadhesha Surolia. 2015. 'Antioxidant activity and electrochemical elucidation of the enigmatic redox behavior of curcumin and its structurally modified analogues', Electrochimica Acta, 151: 574-83.
    連結：
44. Kahai'i, and Saariallio-Kere. 1997. ''.
    連結：
45. Kennedy, W. R., and M. Alter. 2000. 'Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait', J Clin Neuromuscul Dis, 2: 3-5.
    連結：
46. Kerr, J. F., A. H. Wyllie, and A. R. Currie. 1972. 'Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics', Br J Cancer, 26: 239-57.
    連結：
47. Kessenbrock, K., V. Plaks, and Z. Werb. 2010. 'Matrix metalloproteinases: regulators of the tumor microenvironment', Cell, 141: 52-67.
    連結：
48. Kim, H., M. Rafiuddin-Shah, H. C. Tu, J. R. Jeffers, G. P. Zambetti, J. J. Hsieh, and E. H. Cheng. 2006. 'Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies', Nat Cell Biol, 8: 1348-58.
    連結：
49. Kim, J. M., E. M. Noh, K. B. Kwon, J. S. Kim, Y. O. You, J. K. Hwang, B. M. Hwang, B. S. Kim, S. H. Lee, S. J. Lee, S. H. Jung, H. J. Youn, and Y. R. Lee. 2012. 'Curcumin suppresses the TPA-induced invasion through inhibition of PKCalpha-dependent MMP-expression in MCF-7 human breast cancer cells', Phytomedicine, 19: 1085-92.
    連結：
50. Krakstad, C., and M. Chekenya. 2010. 'Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics', Mol Cancer, 9: 135.
    連結：
51. Kukongviriyapan, U., P. Pannangpetch, V. Kukongviriyapan, W. Donpunha, K. Sompamit, and P. Surawattanawan. 2014. 'Curcumin protects against cadmium-induced vascular dysfunction, hypertension and tissue cadmium accumulation in mice', Nutrients, 6: 1194-208.
    連結：
52. La Spada, A. R., E. M. Wilson, D. B. Lubahn, A. E. Harding, and K. H. Fischbeck. 1991. 'Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy', Nature, 352: 77-9.
    連結：
53. Laconi, E., S. Doratiotto, and P. Vineis. 2008. 'The microenvironments of multistage carcinogenesis', Semin Cancer Biol, 18: 322-9.
    連結：
54. Lai, K. P., C. K. Huang, Y. J. Chang, C. Y. Chung, S. Yamashita, L. Li, S. O. Lee, S. Yeh, and C. Chang. 2013. 'New therapeutic approach to suppress castration-resistant prostate cancer using ASC-J9 via targeting androgen receptor in selective prostate cells', Am J Pathol, 182: 460-73.
    連結：
55. Letai, A., M. C. Bassik, L. D. Walensky, M. D. Sorcinelli, S. Weiler, and S. J. Korsmeyer. 2002. 'Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics', Cancer Cell, 2: 183-92.
    連結：
56. Li, F., X. Chen, B. Xu, and H. Zhou. 2015. 'Curcumin induces p53-independent necrosis in H1299 cells via a mitochondria-associated pathway', Mol Med Rep, 12: 7806-14.
    連結：
57. Li, P., D. Nijhawan, I. Budihardjo, S. M. Srinivasula, M. Ahmad, E. S. Alnemri, and X. Wang. 1997. 'Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade', Cell, 91: 479-89.
    連結：
58. Lian, S., Y. Xia, P. N. Khoi, T. T. Ung, H. J. Yoon, N. H. Kim, K. K. Kim, and Y. D. Jung. 2015. 'Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-small ka, CyrillicB, and AP-1 pathways in human endothelial cells', Toxicology, 338: 104-16.
    連結：
59. Lima, R. T., S. Busacca, G. M. Almeida, G. Gaudino, D. A. Fennell, and M. H. Vasconcelos. 2011. 'MicroRNA regulation of core apoptosis pathways in cancer', Eur J Cancer, 47: 163-74.
    連結：
60. Loffek, S., O. Schilling, and C. W. Franzke. 2011. 'Series "matrix metalloproteinases in lung health and disease": Biological role of matrix metalloproteinases: a critical balance', Eur Respir J, 38: 191-208.
    連結：
61. Ma, J., H. Yu, J. Liu, Y. Chen, Q. Wang, and L. Xiang. 2016. 'Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats', Neurosci Lett, 610: 139-43.
    連結：
62. Maheshwari, R. K., A. K. Singh, J. Gaddipati, and R. C. Srimal. 2006. 'Multiple biological activities of curcumin: a short review', Life Sci, 78: 2081-7.
    連結：
63. Mannello, F., F. Luchetti, E. Falcieri, and S. Papa. 2005. 'Multiple roles of matrix metalloproteinases during apoptosis', Apoptosis, 10: 19-24.
    連結：
64. McCampbell, A., and K. H. Fischbeck. 2001. 'Polyglutamine and CBP: fatal attraction?', Nat Med, 7: 528-30.
    連結：
65. McGowan, P. M., and M. J. Duffy. 2008. 'Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database', Ann Oncol, 19: 1566-72.
    連結：
66. Miyamoto, H., Z. Yang, Y. T. Chen, H. Ishiguro, H. Uemura, Y. Kubota, Y. Nagashima, Y. J. Chang, Y. C. Hu, M. Y. Tsai, S. Yeh, E. M. Messing, and C. Chang. 2007. 'Promotion of bladder cancer development and progression by androgen receptor signals', J Natl Cancer Inst, 99: 558-68.
    連結：
67. Mo, N., Z. Q. Li, J. Li, and Y. D. Cao. 2012. 'Curcumin inhibits TGF-beta1-induced MMP-9 and invasion through ERK and Smad signaling in breast cancer MDA- MB-231 cells', Asian Pac J Cancer Prev, 13: 5709-14.
    連結：
68. Mohammadi, R., and H. Mahmoodi. 2013. 'Improvement of peripheral nerve regeneration following nerve repair by silicone tube filled with curcumin: a preliminary study in the rat model', Int J Surg, 11: 819-25.
    連結：
69. Morales, A., D. Eidinger, and A. W. Bruce. 1976. 'Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors', J Urol, 116: 180-3.
    連結：
70. Motoyama, N., F. Wang, K. A. Roth, H. Sawa, K. Nakayama, K. Nakayama, I. Negishi, S. Senju, Q. Zhang, S. Fujii, and et al. 1995. 'Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice', Science, 267: 1506-10.
    連結：
71. Murata, S., K. Yanagisawa, K. Fukunaga, T. Oda, A. Kobayashi, R. Sasaki, and N. Ohkohchi. 2010. 'Fatty acid synthase inhibitor cerulenin suppresses liver metastasis of colon cancer in mice', Cancer Sci, 101: 1861-5.
    連結：
72. Mustacchi, G., and M. De Laurentiis. 2015. 'The role of taxanes in triple-negative breast cancer: literature review', Drug Des Devel Ther, 9: 4303-18.
    連結：
73. Nakayama, K., K. Nakayama, I. Negishi, K. Kuida, Y. Shinkai, M. C. Louie, L. E. Fields, P. J. Lucas, V. Stewart, F. W. Alt, and et al. 1993. 'Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice', Science, 261: 1584-8.
    連結：
74. Opferman, J. T., A. Letai, C. Beard, M. D. Sorcinelli, C. C. Ong, and S. J. Korsmeyer. 2003. 'Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1', Nature, 426: 671-6.
    連結：
75. Overall, C. M., and C. Lopez-Otin. 2002. 'Strategies for MMP inhibition in cancer: innovations for the post-trial era', Nat Rev Cancer, 2: 657-72.
    連結：
76. Peter, M. E., and P. H. Krammer. 2003. 'The CD95(APO-1/Fas) DISC and beyond', Cell Death Differ, 10: 26-35.
    連結：
77. Pittayapruek, P., J. Meephansan, O. Prapapan, M. Komine, and M. Ohtsuki. 2016. 'Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis', Int J Mol Sci, 17.
    連結：
78. Ringel, S. P., N. S. Lava, M. M. Treihaft, M. L. Lubs, and H. A. Lubs. 1978. 'Late-onset X-linked recessive spinal and bulbar muscular atrophy', Muscle Nerve, 1: 297-307.
    連結：
79. Robertson, J. F., A. Howell, A. Buzdar, M. von Euler, and D. Lee. 1999. 'Static disease on anastrozole provides similar benefit as objective response in patients with advanced breast cancer', Breast Cancer Res Treat, 58: 157-62.
    連結：
80. Roy, D. M., and L. A. Walsh. 2014. 'Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors', Breast Cancer (Dove Med Press), 6: 81-91.
    連結：
81. Safarpour, D., and F. A. Tavassoli. 2015. 'A targetable androgen receptor-positive breast cancer subtype hidden among the triple-negative cancers', Arch Pathol Lab Med, 139: 612-7.
    連結：
82. Sestak, I., Y. Zhang, B. E. Schroeder, C. A. Schnabel, M. Dowsett, J. Cuzick, and D. Sgroi. 2016. 'Cross Stratification and Differential Risk by Breast Cancer Index and Recurrence Score in women with hormone receptor positive lymph-node negative early stage breast cancer', Clin Cancer Res.
    連結：
83. Shang, Z., Y. Li, M. Zhang, J. Tian, R. Han, C. R. Shyr, E. Messing, S. Yeh, Y. Niu, and C. Chang. 2015. 'Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression', Mol Cancer Ther, 14: 2586-94.
    連結：
84. Sharpe, J. C., D. Arnoult, and R. J. Youle. 2004. 'Control of mitochondrial permeability by Bcl-2 family members', Biochim Biophys Acta, 1644: 107-13.
    連結：
85. Smith, C. A., T. Farrah, and R. G. Goodwin. 1994. 'The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death', Cell, 76: 959-62.
    連結：
86. Sopher, B. L., P. S. Thomas, Jr., M. A. LaFevre-Bernt, I. E. Holm, S. A. Wilke, C. B. Ware, L. W. Jin, R. T. Libby, L. M. Ellerby, and A. R. La Spada. 2004. 'Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration', Neuron, 41: 687-99.
    連結：
87. Steward, W. P., and A. J. Gescher. 2008. 'Curcumin in cancer management: recent results of analogue design and clinical studies and desirable future research', Mol Nutr Food Res, 52: 1005-9.
    連結：
88. Strasser, A. 2005. 'The role of BH3-only proteins in the immune system', Nat Rev Immunol, 5: 189-200.
    連結：
89. Strasser, A., L. O'Connor, and V. M. Dixit. 2000. 'Apoptosis signaling', Annu Rev Biochem, 69: 217-45.
    連結：
90. Strasser, A., and M. Pellegrini. 2004. 'T-lymphocyte death during shutdown of an immune response', Trends Immunol, 25: 610-5.
    連結：
91. Sun, L. N., Z. Y. Yang, S. S. Lv, X. C. Liu, G. J. Guan, and G. Liu. 2014. 'Curcumin prevents diabetic nephropathy against inflammatory response via reversing caveolin-1 Tyr14 phosphorylation influenced TLR4 activation', Int Immunopharmacol, 23: 236-46.
    連結：
92. Sunagawa, Y., H. Wada, H. Suzuki, H. Sasaki, A. Imaizumi, H. Fukuda, T. Hashimoto, Y. Katanasaka, A. Shimatsu, T. Kimura, H. Kakeya, M. Fujita, K. Hasegawa, and T. Morimoto. 2012. 'A novel drug delivery system of oral curcumin markedly improves efficacy of treatment for heart failure after myocardial infarction in rats', Biol Pharm Bull, 35: 139-44.
    連結：
93. Sympson, C. J., R. S. Talhouk, C. M. Alexander, J. R. Chin, S. M. Clift, M. J. Bissell, and Z. Werb. 1994. 'Targeted expression of stromelysin-1 in mammary gland provides evidence for a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression', J Cell Biol, 125: 681-93.
    連結：
94. Tamvakopoulos, C., K. Dimas, Z. D. Sofianos, S. Hatziantoniou, Z. Han, Z. L. Liu, J. H. Wyche, and P. Pantazis. 2007. 'Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin', Clin Cancer Res, 13: 1269-77.
    連結：
95. Tang, Y., Y. Wang, M. F. Kiani, and B. Wang. 2016. 'Classification, Treatment Strategy, and Associated Drug Resistance in Breast Cancer', Clin Breast Cancer.
    連結：
96. Tapia, E., V. Soto, K. M. Ortiz-Vega, G. Zarco-Marquez, E. Molina-Jijon, M. Cristobal-Garcia, J. Santamaria, W. R. Garcia-Nino, F. Correa, C. Zazueta, and J. Pedraza-Chaverri. 2012. 'Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats', Oxid Med Cell Longev, 2012: 269039.
    連結：
97. van Loo, G., X. Saelens, M. van Gurp, M. MacFarlane, S. J. Martin, and P. Vandenabeele. 2002. 'The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet', Cell Death Differ, 9: 1031-42.
    連結：
98. Veis, D. J., C. M. Sorenson, J. R. Shutter, and S. J. Korsmeyer. 1993. 'Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair', Cell, 75: 229-40.
    連結：
99. Verbrugge, I., R. W. Johnstone, and M. J. Smyth. 2010. 'SnapShot: Extrinsic apoptosis pathways', Cell, 143: 1192, 92.e1-2.
    連結：
100. Vineis, P., A. Schatzkin, and J. D. Potter. 2010. 'Models of carcinogenesis: an overview', Carcinogenesis, 31: 1703-9.
     連結：
101. Vu, T. H., J. M. Shipley, G. Bergers, J. E. Berger, J. A. Helms, D. Hanahan, S. D. Shapiro, R. M. Senior, and Z. Werb. 1998. 'MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes', Cell, 93: 411-22.
     連結：
102. Wakil, S. J. 1989. 'Fatty acid synthase, a proficient multifunctional enzyme', Biochemistry, 28: 4523-30.
     連結：
103. Walensky, L. D. 2006. 'BCL-2 in the crosshairs: tipping the balance of life and death', Cell Death Differ, 13: 1339-50.
     連結：
104. Wen, S., Y. Niu, S. O. Lee, S. Yeh, Z. Shang, H. Gao, Y. Li, F. Chou, and C. Chang. 2016. 'Targeting fatty acid synthase with ASC-J9 suppresses proliferation and invasion of prostate cancer cells', Mol Carcinog.
     連結：
105. Westermarck, J., and V. M. Kahari. 1999. 'Regulation of matrix metalloproteinase expression in tumor invasion', Faseb j, 13: 781-92.
     連結：
106. Willis, S. N., L. Chen, G. Dewson, A. Wei, E. Naik, J. I. Fletcher, J. M. Adams, and D. C. Huang. 2005. 'Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins', Genes Dev, 19: 1294-305.
     連結：
107. Willis, S. N., J. I. Fletcher, T. Kaufmann, M. F. van Delft, L. Chen, P. E. Czabotar, H. Ierino, E. F. Lee, W. D. Fairlie, P. Bouillet, A. Strasser, R. M. Kluck, J. M. Adams, and D. C. Huang. 2007. 'Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak', Science, 315: 856-9.
     連結：
108. Wu, D., J. Xu, G. Yu, B. Zhang, H. Wang, C. Wang, G. Ru, A. Sun, L. Shen, and Q. Wei. 2013. 'Expression status of fatty acid synthase (FAS) but not HER2 is correlated with the differentiation grade and prognosis of esophageal carcinoma', Hepatogastroenterology, 60: 99-106.
     連結：
109. Xu, L., H. Ning, L. Gu, Q. Wang, W. Lu, H. Peng, W. Cui, B. Ying, C. R. Ross, G. M. Wilson, L. Wei, W. S. Wold, and J. Liu. 2015. 'Tristetraprolin induces cell cycle arrest in breast tumor cells through targeting AP-1/c-Jun and NF-kappaB pathway', Oncotarget, 6: 41679-91.
     連結：
110. Xu, Y., S. Huang, Z. G. Liu, and J. Han. 2006. 'Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1/TRAF2-mediated JNK1 activation', J Biol Chem, 281: 8788-95.
     連結：
111. Xue, X., J. L. Yu, D. Q. Sun, F. Kong, X. J. Qu, W. Zou, J. Wu, and R. M. Wang. 2014. 'Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via regulation of mitochondrial signaling pathways', Asian Pac J Cancer Prev, 15: 3987-92.
     連結：
112. Yang, Z., Y. J. Chang, I. C. Yu, S. Yeh, C. C. Wu, H. Miyamoto, D. E. Merry, G. Sobue, L. M. Chen, S. S. Chang, and C. Chang. 2007. 'ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor', Nat Med, 13: 348-53.
     連結：
113. Yin, X. M., Z. N. Oltvai, and S. J. Korsmeyer. 1994. 'BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax', Nature, 369: 321-3.
     連結：
114. Yuan, X., H. Li, H. Bai, Z. Su, Q. Xiang, C. Wang, B. Zhao, Y. Zhang, Q. Zhang, Y. Chu, and Y. Huang. 2014. 'Synthesis of novel curcumin analogues for inhibition of 11beta-hydroxysteroid dehydrogenase type 1 with anti-diabetic properties', Eur J Med Chem, 77: 223-30.
     連結：
115. Zaytseva, Y. Y., P. G. Rychahou, P. Gulhati, V. A. Elliott, W. C. Mustain, K. O'Connor, A. J. Morris, M. Sunkara, H. L. Weiss, E. Y. Lee, and B. M. Evers. 2012. 'Inhibition of fatty acid synthase attenuates CD44-associated signaling and reduces metastasis in colorectal cancer', Cancer Res, 72: 1504-17.
     連結：
116. Zeichner, S. B., H. Terawaki, and K. Gogineni. 2016. 'A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer', Breast Cancer (Auckl), 10: 25-36.
     連結：
117. Brady-West, D. C., and D. A. McGrowder. 2011. 'Triple negative breast cancer: therapeutic and prognostic implications', Asian Pac J Cancer Prev, 12: 2139-43.
118. Cao, F., T. Liu, Y. Xu, D. Xu, and S. Feng. 2015. 'Curcumin inhibits cell proliferation and promotes apoptosis in human osteoclastoma cell through MMP-9, NF-kappaB and JNK signaling pathways', Int J Clin Exp Pathol, 8: 6037-45.
119. Chittenden, T., C. Flemington, A. B. Houghton, R. G. Ebb, G. J. Gallo, B. Elangovan, G. Chinnadurai, and R. J. Lutz. 1995. 'A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions', Embo j, 14: 5589-96.
120. Curtis, C., S. P. Shah, S. F. Chin, G. Turashvili, O. M. Rueda, M. J. Dunning, D. Speed, A. G. Lynch, S. Samarajiwa, Y. Yuan, S. Graf, G. Ha, G. Haffari, A. Bashashati, R. Russell, S. McKinney, A. Langerod, A. Green, E. Provenzano, G. Wishart, S. Pinder, P. Watson, F. Markowetz, L. Murphy, I. Ellis, A. Purushotham, A. L. Borresen-Dale, J. D. Brenton, S. Tavare, C. Caldas, and S. Aparicio. 2012. 'The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups', Nature, 486: 346-52.
121. Danial, N. N., and S. J. Korsmeyer. 2004. 'Cell death: critical control points', Cell, 116: 205-19.
122. Daniel, P., A. Leutz, and M. Lipp. 2009. 'The signalling pathway of BimL and BimS, two isoforms of the BH3-only protein Bim, in apoptosis'.
123. Gack, S., R. Vallon, J. Schmidt, A. Grigoriadis, J. Tuckermann, J. Schenkel, H. Weiher, E. F. Wagner, and P. Angel. 1995. 'Expression of interstitial collagenase during skeletal development of the mouse is restricted to osteoblast-like cells and hypertrophic chondrocytes', Cell Growth Differ, 6: 759-67.
124. Gavathiotis, E., M. Suzuki, M. L. Davis, K. Pitter, G. H. Bird, S. G. Katz, H. C. Tu, H. Kim, E. H. Cheng, N. Tjandra, and L. D. Walensky. 2008. 'BAX activation is initiated at a novel interaction site', Nature, 455: 1076-81.
125. Lindsten, T., A. J. Ross, A. King, W. X. Zong, J. C. Rathmell, H. A. Shiels, E. Ulrich, K. G. Waymire, P. Mahar, K. Frauwirth, Y. Chen, M. Wei, V. M. Eng, D. M. Adelman, M. C. Simon, A. Ma, J. A. Golden, G. Evan, S. J. Korsmeyer, G. R. MacGregor, and C. B. Thompson. 2000. 'The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues', Mol Cell, 6: 1389-99.
126. van de Vijver, M. J., Y. D. He, L. J. van't Veer, H. Dai, A. A. Hart, D. W. Voskuil, G. J. Schreiber, J. L. Peterse, C. Roberts, M. J. Marton, M. Parrish, D. Atsma, A. Witteveen, A. Glas, L. Delahaye, T. van der Velde, H. Bartelink, S. Rodenhuis, E. T. Rutgers, S. H. Friend, and R. Bernards. 2002. 'A gene-expression signature as a predictor of survival in breast cancer', N Engl J Med, 347: 1999-2009.
127. Wang, X. 2001. 'The expanding role of mitochondria in apoptosis', Genes Dev, 15: 2922-33.
128. Witty, J. P., T. Lempka, R. J. Coffey, Jr., and L. M. Matrisian. 1995. 'Decreased tumor formation in 7,12-dimethylbenzanthracene-treated stromelysin-1 transgenic mice is associated with alterations in mammary epithelial cell apoptosis', Cancer Res, 55: 1401-6.