DOI QR코드

DOI QR Code

Esculetin의 caspase-3 활성을 통한 U937 인체 혈구암세포의 세포사멸 유도

Esculetin Induces Apoptosis through Caspase-3 Activation in Human Leukemia U937 Cells

  • 박철 (동의대학교 블루바이오 소재개발센터) ;
  • 현숙경 (동의대학교 블루바이오 소재개발센터) ;
  • 신우진 (동의대학교 한의과대학 내과학교실) ;
  • 정경태 (동의대학교 블루바이오 소재개발센터) ;
  • 최병태 (부산대학교 한의학전문대학원 해부학교실) ;
  • 권현주 (동의대학교 블루바이오 소재개발센터) ;
  • 황혜진 (동의대학교 블루바이오 소재개발센터) ;
  • 김병우 (동의대학교 블루바이오 소재개발센터) ;
  • 박동일 (동의대학교 한의과대학 내과학교실) ;
  • 이원호 (부산대학교 자연과학대학 생물학과) ;
  • 최영현 (동의대학교 블루바이오 소재개발센터)
  • Park, Cheol (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Hyun, Sook-Kyung (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Shin, Woo-Jin (Departments of Physiology, College of Oriental Medicine, Dong-Eui University) ;
  • Chung, Kyung-Tae (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Choi, Byung-Tae (Division of Meridian and Structural Medicine, School of Oriental Medicine, Pusan National University) ;
  • Kwon, Hyun-Ju (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Hwang, Hye-Jin (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Kim, Byung-Woo (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Park, Dong-Il (Departments of Physiology, College of Oriental Medicine, Dong-Eui University) ;
  • Lee, Won-Ho (Department of Biology, College of Natural Sciences, Pusan National University) ;
  • Choi, Yung-Hyun (Blue-Bio Industry RIC, Dong-Eui University)
  • 발행 : 2009.02.28

초록

Esculetin, a coumarin compound, has been known to inhibit proliferation and induce apoptosis in several types of human cancer cells. However, the molecular mechanisms involved in esculetin-induced apoptosis are still uncharacterized in human leukemia cells. In this study, we have investigated whether esculetin exerts anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that esculetin could inhibit cell viability in a time-dependent manner, which was associated with the induction of apoptotic cell death such as increased populations of apoptotic- sub G1 phase. Apoptosis of U937 cells by esculetin was associated with an inhibition of Bcl-2/Bax binding activity, formation of tBid, down-regulation of X-linked inhibitor of apoptotic protein (XIAP) expression, and up-regulation of death receptor 4 (DR4) and FasL expression. Esculetin treatment also induced the degradation of ${\beta}$-catenin and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthermore, a caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited sub-G1 phase DNA content, morphological changes and degradation of ${\beta}$-catenin and DEE45/ICAD. These results indicated that a key regulator in esculetin-induced apoptosis was caspase-3 in human leukemia U937 cells.

키워드

참고문헌

  1. Algeciras-Schimnich, A., E. M. Pietras, B. C. Barnhart, P. Legembre, S. Vijayan, S. L. Holbeck, and M. E. Peter. 2003. Two CD95 tumor classes with different sensitivities to antitumor drugs. Proc. Natl. Acad. Sci. USA 100, 11445-11450 https://doi.org/10.1073/pnas.2034995100
  2. Ashkenazi, A. 2002. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat. Rev. Cancer 2, 420-430 https://doi.org/10.1038/nrc821
  3. Bratton, S. B., G. Walker, S. M. Srinivasula, X. M. Sun, M.Butterworth, E. S. Alnemri, and G. M. Cohen. 2001. Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes.EMBO J. 20, 998-1009 https://doi.org/10.1093/emboj/20.5.998
  4. Coultas, L. and A. Strasser. 2003. The role of the Bcl-2 protein family in cancer. Semin. Cancer Biol. 13, 115-123 https://doi.org/10.1016/S1044-579X(02)00129-3
  5. Debatin, K. M. and P. H. Krammer. 2004. Death receptors in chemotherapy and cancer. Oncogene 23, 2950-2966 https://doi.org/10.1038/sj.onc.1207558
  6. Donovan, M. and T. G. Cotter. 2004. Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death. Biochim. Biophys. Acta. 1644, 133-147 https://doi.org/10.1016/j.bbamcr.2003.08.011
  7. Evans, V. G. 1993. Multiple pathways to apoptosis. Cell Biol. Int. 17, 461-476 https://doi.org/10.1006/cbir.1993.1087
  8. Fukuda, K. 1999. Apoptosis-associated cleavage of$\beta$-catenin in human colon cancer and rat hepatoma cells. Int. J. Biochem. Cell Biol. 31, 519-529 https://doi.org/10.1016/S1357-2725(98)00119-8
  9. Fulda, S. and K. M. Debatin. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798-4811 https://doi.org/10.1038/sj.onc.1209608
  10. Han, S. I., Y. S. Kim, and T. H. Kim. 2008. Role of apoptotic and necrotic cell death under physiologic conditions. BMB Rep. 41, 1-10 https://doi.org/10.5483/BMBRep.2008.41.1.001
  11. Hecht, S. S., P. M. Kenney, M. Wang, N. Trushin, S. Agarwal, A. V. Rao, and P. Upadhyaya. 1999. Evaluation of butylated hydroxyanisole, myo-inositol, curcumin, esculetin, resveratrol andlycopene as inhibitors of benzo[a]pyreneplus 4-(methylnitrosamino) 1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. Cancer Lett. 137, 123-130 https://doi.org/10.1016/S0304-3835(98)00326-7
  12. Holcik, M., H. Gibson, and R. G. Korneluk. 2001. XIAP: apoptotic brake and promising therapeutic target. Apoptosis 6, 253-261 https://doi.org/10.1023/A:1011379307472
  13. Jin, Z. and W. S. El-Deiry. 2005. Overview of cell death signaling pathways. Cancer Biol. Ther. 4, 139-163 https://doi.org/10.4161/cbt.4.2.1508
  14. 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, 239-257 https://doi.org/10.1038/bjc.1972.33
  15. Kimberley, F. C. and G. R. Screaton. 2004. Following a TRAIL: update on a ligand and its five receptors. Cell Res. 14, 359-372 https://doi.org/10.1038/sj.cr.7290236
  16. Kuo, H. C., H. J. Lee, C. C. Hu, H. I. Shun, and T. H. Tseng. 2006. Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells. Toxicol. Appl. Pharmacol. 210, 55-62 https://doi.org/10.1016/j.taap.2005.06.020
  17. Lee, S. H., C. Park, C. Y. Jin, G. Y. Kim, S. K. Moon, J. W. Hyun, W. H. Lee, B. T. Choi, T. K. Kwon, Y. H. Yoo, and Y. H. Choi. 2008. Involvement of extracellular signal-related kinase signaling in esculetin induced G1 arrest of human leukemia U937 cells. Biomed. Pharmacother. 62, 723-729 https://doi.org/10.1016/j.biopha.2007.12.001
  18. Letai, A. 2005. Pharmacological manipulation of Bcl-2 family members to control cell death. J. Clin. Invest. 115, 2648-2655 https://doi.org/10.1172/JCI26250
  19. Li, H., H. Zhu, C. J. Xu, and J. Yuan. 1998. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501 https://doi.org/10.1016/S0092-8674(00)81590-1
  20. Matsunaga, K., N. Yoshimi, Y. Yamada, M. Shimizu, K. Kawabata, Y. Ozawa, A. Hara, and H. Mori. 1998. Inhibitory effects of nabumetone, a cyclooxygenase-2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N-methyl-N-nitrosourea- induced mammary carcinogenesis in rats. Jpn. J. Cancer Res. 89, 496-501
  21. Okada, H. and T. W. Mak. 2004. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer 4, 592-603 https://doi.org/10.1038/nrc1412
  22. Okada, Y., N. Miyauchi, K. Suzuki, T. Kobayashi, C. Tsutsui, K. Mayuzumi, S. Nishibe, and T. Okuyama. 1995. Search for naturally occurring substances to prevent the complications of diabetes. II. Inhibitory effect of coumarin and flavonoid derivatives on bovine lens aldose reductase and rabbit platelet aggregation. Chem. Pharm. Bull. (Tokyo) 43, 1385-1387 https://doi.org/10.1248/cpb.43.1385
  23. Park, C., C. Y. Jin, G. Y. Kim, I. W. Choi, T. K. Kwon, B. T. Choi, S. J. Lee, W. H. Lee, and Y. H. Choi. 2008. Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK. Toxicol. Appl. Pharmacol. 227, 219-228 https://doi.org/10.1016/j.taap.2007.10.003
  24. Petak, I. and J. A. Houghton. 2001. Shared pathways: death receptors and cytotoxic drugs in cancer therapy. Pathol. Oncol. Res. 7, 95-106 https://doi.org/10.1007/BF03032574
  25. Rosse, T., R. Olivier, L. Monney, M. Rager, S. Conus, I. Fellay, B. Jansen, and C. Borner. 1998. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 391, 496-499 https://doi.org/10.1038/35160
  26. Salvesen, G. S. and C. S. Duckett. 2002. IAP proteins: blocking the road to death's door. Nat. Rev. Mol. Cell Biol. 3, 401-410 https://doi.org/10.1038/nrm830
  27. Wang, C. J., Y. J. Hsieh, C. Y. Chu, Y. L. Lin, and T. H. Tseng. 2002. Inhibition of cell cycle progression in human leukemia HL-60 cells by esculetin. Cancer Lett. 183, 163-168 https://doi.org/10.1016/S0304-3835(02)00031-9
  28. Widlak, P, and W. T. Garrard. 2005. Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G. J. Cell Biochem. 94, 1078-1087 https://doi.org/10.1002/jcb.20409
  29. Widlak, P. 2000. The DFF40/CAD endonuclease and its role in apoptosis. Acta. Biochim. Pol. 47, 1037-1044 https://doi.org/10.1093/nar/gkm486
  30. Wijnhoven, B. P., W. N. Dinjens, and M. Pignatelli. 2000. E-cadherin-catenin cell-cell adhesion complex and human cancer. Br. J. Surg. 87, 992-1005 https://doi.org/10.1046/j.1365-2168.2000.01513.x
  31. Zou, H., Y. Li, X. Liu, and X. Wang. 1999. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem. 274, 11549-11556 https://doi.org/10.1074/jbc.274.17.11549

피인용 문헌

  1. Induction of Apoptosis by Ethanol Extracts of Fermented Agabeans in AGS Human Gastric Carcinoma Cells vol.20, pp.12, 2010, https://doi.org/10.5352/JLS.2010.20.12.1872