Please use this identifier to cite or link to this item:
標題: 蘆薈大黃素對舌咽癌細胞株之凋亡和侵犯機制的影響
The Effects of Aloe-Emodin on Apoptosis and Invasion of the Pharyngeal Squamous Carcinoma Cell Line
作者: 張兆嶔
Chang, Chao-Chin
關鍵字: 蘆薈大黃素
aloe emodin
出版社: 生命科學系所
引用: 1.Afford, S., and S. Randhawa. 2000. Apoptosis. Mol Pathol 53:55-63. 2.Agarwal, S. K., S. S. Singh, S. Verma, and S. Kumar. 2000. Antifungal activity of anthraquinone derivatives from Rheum emodi. J Ethnopharmacol 72:43-6. 3.Andersen, D. O., N. D. Weber, S. G. Wood, B. G. Hughes, B. K. Murray, and J. A. North. 1991. In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. Antiviral Res 16:185-96. 4.Arosio, B., N. Gagliano, L. M. Fusaro, L. Parmeggiani, J. Tagliabue, P. Galetti, D. De Castri, C. Moscheni, and G. Annoni. 2000. Aloe-Emodin quinone pretreatment reduces acute liver injury induced by carbon tetrachloride. Pharmacol Toxicol 87:229-33. 5.Bae, J. H., J. W. Park, and T. K. Kwon. 2003. Ruthenium red, inhibitor of mitochondrial Ca2+ uniporter, inhibits curcumin-induced apoptosis via the prevention of intracellular Ca2+ depletion and cytochrome c release. Biochem Biophys Res Commun 303:1073-9. 6.Bhatia, N., C. Agarwal, and R. Agarwal. 2001. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells. Nutr Cancer 39:292-9. 7.Chen, S. H., K. Y. Lin, C. C. Chang, C. L. Fang, and C. P. Lin. 2007. Aloe-emodin-induced apoptosis in human gastric carcinoma cells. Food Chem Toxicol 45:2296-303. 8.De La Puerta, R., E. Martinez, L. Bravo, and M. C. Ahumada. 1996. Effect of silymarin on different acute inflammation models and on leukocyte migration. J Pharm Pharmacol 48:968-70. 9.DeLaney, T. F., N. Afridi, A. G. Taghian, D. A. Sanders, N. S. Fuleihan, D. V. Faller, and C. P. Nogueira. 1996. 13-cis-retinoic acid with alpha-2a-interferon enhances radiation cytotoxicity in head and neck squamous cell carcinoma in vitro. Cancer Res 56:2277-80. 10.Fairbairn, J. W. 1980. Natural anthraquinone drugs. Pharmacology 20:2–122. 11.Guruprasad, L., V. Dhanaraj, D. Timm, T. L. Blundell, I. Gout, and M. D. Waterfield. 1995. The crystal structure of the N-terminal SH3 domain of Grb2. J Mol Biol 248:856-66. 12.H.Lodish, A. B. 2003. Molekular Cell Biology. W. H. Freeman 5.Editon:953. 13.Han, Z., D. Chatterjee, J. Early, P. Pantazis, E. A. Hendrickson, and J. H. Wyche. 1996. Isolation and characterization of an apoptosis-resistant variant of human leukemia HL-60 cells that has switched expression from Bcl-2 to Bcl-xL. Cancer Res 56:1621-8. 14.Hatano, T., H. Uebayashi, H. Ito, S. Shiota, T. Tsuchiya, and T. Yoshida. 1999. Phenolic constituents of Cassia seeds and antibacterial effect of some naphthalenes and anthraquinones on methicillin-resistant Staphylococcus aureus. Chem Pharm Bull (Tokyo) 47:1121-7. 15.He, T. P., W. H. Yan, L. E. Mo, and N. C. Liang. 2008. Inhibitory effect of aloe-emodin on metastasis potential in HO-8910PM cell line. J Asian Nat Prod Res 10:383-90. 16.Hengartner, M. O. 2000. The biochemistry of apoptosis. Nature 407:770-6. 17.Ibrado, A. M., Y. Huang, G. Fang, L. Liu, and K. Bhalla. 1996. Overexpression of Bcl-2 or Bcl-xL inhibits Ara-C-induced CPP32/Yama protease activity and apoptosis of human acute myelogenous leukemia HL-60 cells. Cancer Res 56:4743-8. 18.Igney, F. H., and P. H. Krammer. 2002. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2:277-88. 19.Jurgensmeier, J. M., Z. Xie, Q. Deveraux, L. Ellerby, D. Bredesen, and J. C. Reed. 1998. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A 95:4997-5002. 20.Kelekar, A., and C. B. Thompson. 1998. Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8:324-30. 21.Komoriya, A., B. Z. Packard, M. J. Brown, M. L. Wu, and P. A. Henkart. 2000. Assessment of caspase activities in intact apoptotic thymocytes using cell-permeable fluorogenic caspase substrates. J Exp Med 191:1819-28. 22.Krammer, P. H. 1999. CD95(APO-1/Fas)-mediated apoptosis: live and let die. Adv. Immunol. 71:163-210 23.Krumbiegel, G., and H. U. Schulz. 1993. Rhein and aloe-emodin kinetics from senna laxatives in man. Pharmacology 47 Suppl 1:120-4. 24.Lee, J. T., Jr., and J. A. McCubrey. 2002. The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia. Leukemia 16:486-507. 25.Lin, J. G., G. W. Chen, T. M. Li, S. T. Chouh, T. W. Tan, and J. G. Chung. 2006. Aloe-emodin induces apoptosis in T24 human bladder cancer cells through the p53 dependent apoptotic pathway. J Urol 175:343-7. 26.Lin, X. H., H. Y. Wan, Y. F. Zhang, and J. H. Chen. 2008. Studies of the interaction between Aloe-emodin and DNA and preparation of DNA biosensor for detection of PML-RARalpha fusion gene in acute promyelocytic leukemia. Talanta 74:944-50. 27.McDonnell, T. J., A. Beham, M. Sarkiss, M. M. Andersen, and P. Lo. 1996. Importance of the Bcl-2 family in cell death regulation. Experientia 52:1008-17. 28.Mijatovic, S., D. Maksimovic-Ivanic, J. Radovic, D. Miljkovic, L. Harhaji, O. Vuckovic, S. Stosic-Grujicic, M. Mostarica Stojkovic, and V. Trajkovic. 2005. Anti-glioma action of aloe emodin: the role of ERK inhibition. Cell Mol Life Sci 62:589-98. 29.Nabeshima, K., T. Inoue, Y. Shimao, and T. Sameshima. 2002. Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int 52:255-64. 30.Nakagawa, Y., S. Okada, M. Hatano, M. Ebara, H. Saisho, and T. Tokuhisa. 2002. Downregulation of bcl-xL is relevant to UV-induced apoptosis in fibroblasts. J Biochem Mol Biol 35:452-8. 31.Pecere, T., M. V. Gazzola, C. Mucignat, C. Parolin, F. D. Vecchia, A. Cavaggioni, G. Basso, A. Diaspro, B. Salvato, M. Carli, and G. Palu. 2000. Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors. Cancer Res 60:2800-4. 32.Petit, P. X., J. E. O''Connor, D. Grunwald, and S. C. Brown. 1990. Analysis of the membrane potential of rat- and mouse-liver mitochondria by flow cytometry and possible applications. Eur J Biochem 194:389-97. 33.Puil, L., J. Liu, G. Gish, G. Mbamalu, D. Bowtell, P. G. Pelicci, R. Arlinghaus, and T. Pawson. 1994. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. Embo J 13:764-73. 34.Rangan, S. R. 1972. A new human cell line (FaDu) from a hypopharyngeal carcinoma. Cancer 29:117-21. 35.Rathmell, J. C., and C. B. Thompson. 1999. The central effectors of cell death in the immune system. Annu Rev Immunol 17:781-828. 36.Reed, J. C. 1997. Double identity for proteins of the Bcl-2 family. Nature 387:773-6. 37.Reed, J. C., H. Zha, C. Aime-Sempe, S. Takayama, and H. G. Wang. 1996. Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death. Adv Exp Med Biol 406:99-112. 38.Reynolds, T. 1985. The compounds in Aloe leaf exudates: a review. Bot. J. Linn. Soc 90:157–177. 39.Royall, J. A., and H. Ischiropoulos. 1993. Evaluation of 2'',7''-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. Arch Biochem Biophys 302:348-55. 40.Savill, J., and V. Fadok. 2000. Corpse clearance defines the meaning of cell death. Nature 407:784-8. 41.Schmitz, I., S. Kirchhoff, and P. H. Krammer. 2000. Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol 32:1123-36. 42.Singh, R. P., and R. Agarwal. 2002. Flavonoid antioxidant silymarin and skin cancer. Antioxid Redox Signal 4:655-63. 43.Tsujimoto, Y., J. Cossman, E. Jaffe, and C. M. Croce. 1985. Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440-3. 44.Xiang, J., D. T. Chao, and S. J. Korsmeyer. 1996. BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases. Proc Natl Acad Sci U S A 93:14559-63. 45.朱奕. 2001. 二十一世紀:中藥發展面臨重大突破. 紫荊. 46.行政院衛生署統計室. 2007. 衛生統計重要指標九十六年版. 47.張哲壽. 1993. 口腔癌之手術治療及預後. 防癌雜誌 6. 48.黃湧澧. 1990. 南台灣口腔粘膜下纖維化(癌前病兆)之研究. 中華牙醫學會雜誌.
摘要: 雖然有證據證明蘆薈大黃素具有成為抗癌藥物的潛力,但蘆薈大黃素引起人類舌咽癌細胞株凋亡的機制卻尚未瞭解。在本篇研究中首先證實了蘆薈大黃素能夠抑制舌咽癌細胞株的增生並且誘發其凋亡,在蘆薈大黃素所引發的細胞凋亡中可以清楚的觀察到細胞核的濃縮與染色體的裂解,蘆薈大黃素所引起的細胞凋亡伴隨著Bax表現量的上升和Bcl-XL表現量的下降,而Bcl-2的表現量則無顯著變化。在以蘆薈大黃素處理過的舌咽癌細胞中還觀察到caspase-3活性的提高,粒線體膜電位下降,造成cytochrome c和AIF自粒線體轉位至細胞質,並且提高了細胞質中ROS和鈣離子的含量。這些結果說明了蘆薈大黃素在舌咽癌細胞中經由粒線體所調控的途徑誘發舌咽癌細胞進行細胞凋亡;另外,它還能藉由降低MAPK訊息傳導路徑中上游重要的蛋白質的表現量,如Grb2和SOS1,使得下游的轉錄因子調控的基因,如MMP-9,的表現量下降,進一步造成癌細胞移轉的能力下降。以上結果說明了蘆薈大黃素可能作為一種有效治療舌咽癌細胞的抗癌藥物。
Although there are evidences showing that aloe-emodin might be a potential anticancer drug, but the mechanisms that involved in its action on the induction of apoptosis in human pharyngeal squamous carcinoma(PSC)cells are remained to defined. In the present study, we first demonstrated that aloe-emodin could inhibit proliferation and induce apoptosis in PSC cells. Aloe-emodin-induced apoptosis was clearly verified by the appearance of nuclear condensation and DNA fragmentation. Apoptosis induced by aloe-emodin was accompanied by the up-regulation of Bax and down-regulation of Bcl-XL, but no effect on the level of Bcl-2. A significant increase in caspase-3 activity was observed in aloe-emodin treated PSC cells. Moreover, we found that aloe-emodin induced the loss of mitochondrial membrane potential(MMP), the release of cytochrome c and apoptosis-inducing factor(AIF)from mitochondria to cytosol. And also resulted in an elevation of reactive oxygen species (ROS) and increase calcium (Ca++) level in cytosol. In addition to inducing apoptosis, aloe-emodin inhibited the expressions of important proteins in Ras-MAPK signaling pathway, Grb2 and SOS1, and the genes regulated by the signaling pathway were suppressed. As the genes regulated by Ras-MAPK signaling pathway, MMP-9 and VEGF, were down-regulated, the invasion activity of cancer cells was suppressed. These results suggest that aloe-emodin induced apoptosis and inhibited invasion in PSC cells were mediated through mitochondria dependent and Ras-MAPK pathways. It implies the possibility that aloe-emodin could be a useful anticancer agent for treatment of PSC.
其他識別: U0005-2608200811503000
Appears in Collections:生命科學系所



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.