DOI QR코드

DOI QR Code

Cell Death of Human Promyelocytic Leukemia Cell after Low Dose of Electron Beam Irradiation with TNF-α

저 농도의 전자선을 조사한 전골수구성 백혈병 세포 죽음에서의 TNF-α 작용 효과

  • 김동현 (부산가톨릭대학교 방사선학과) ;
  • 고성진 (부산가톨릭대학교 방사선학과)
  • Received : 2014.05.07
  • Accepted : 2014.05.28
  • Published : 2014.06.28

Abstract

Acute promyelocytic leukemia (APL) is a cancer of the blood. Although electron beam (EB) irradiation is used with other anti-cancer agents, EB irradiation can be harmful to normal tissues around the cancer. In the present study, we evaluate the differential cytotoxic effect of EB irradiation with other molecules, including TNF-${\alpha}$, on DMSO-treated HL-60 cells and HL-60 cells. HL-60 cells are the human promyleocytic leukemia cell line and are differentiated by DMSO. DMSO-treated HL-60 cells are considered to be normal granulocytic cells. In these results, TNF-${\alpha}$ may be used as the potential agent for the treatment of blood cancer without side effects in low dose of EB irradiation therapy.

급성전골수구성 백혈병(Acute promyelocytic leukemia, APL)은 혈액암으로 치료가 쉽지 않을 뿐만 아니라 항암치료에 가장 효과가 좋다는 방사선 치료를 해도 오히려 정상세포에도 작용하여 부작용을 초래하게 된다. 본 연구에서는 전자선(EB)을 TNF-${\alpha}$와 같이 처리하였을 경우 정상세포와 암세포의 세포 죽음에 어떠한 영향을 미치는지 확인하였다. HL-60세포는 APL세포주로서 사용하였고 DMSO를 처리하여 분화시킨 HL-60세포는 정상과립구의 성질을 나타내어 정상대조군으로 이용하였다. 그 결과 TNF-${\alpha}$를 전자선을 처리한 HL-60세포에서만 세포독성효과를 나타내었고 이 과정에서 TNF-${\alpha}$는 caspase3를 활성화 시켜서 세포자멸사를 유도하여 세포가 죽음에 이르게 하였다. 결론적으로 TNF-${\alpha}$는 항암치료의 부작용을 없애기 위해 저농도의 전자선 치료 시 함께 사용하여 암 세포의 제거를 증가시켜 암의 치료효율을 높일 수 있는 유효물질로 사료된다.

Keywords

References

  1. R. W. Johnstone, A. A. Ruefli, and S. W. Lowe, "Apoptosis: a link between cancer genetics and chemotherapy," Cell, Vol.8, pp.153-164, 2002(10).
  2. M. S. "Tallman Retinoic acid syndrome: a problem of the past?," Leukemia, Vol.16, pp.160-161,2002. https://doi.org/10.1038/sj.leu.2402344
  3. R. E. Callard and A. J. Yates, "Immunology and mathematics: Crossing the divide," Immunology, Vol.115, pp.21-33, 2005. https://doi.org/10.1111/j.1365-2567.2005.02142.x
  4. V. Baud and M. Karin, "Signal transduction by tumor necrosis factor and its relatives," Trends Cell Biol, Vol.11, pp.372-377, 2001. https://doi.org/10.1016/S0962-8924(01)02064-5
  5. H. Wajant, K. Pfizenmaier, and P. Scheurich, "Tumor necrosis factor signaling," Cell Death Diff, Vol.10, pp.45-65, 2003. https://doi.org/10.1038/sj.cdd.4401189
  6. D. Wallach, "Cell death induction by TNF: A matter of self control," Trends Biochem Sci., Vol.22, pp.107-109, 1997. https://doi.org/10.1016/S0968-0004(97)01015-3
  7. D. Wallach, A. V. Kovalenko, E. E. Varfolomeev, and M. P. Boldin, "Death-inducing functions of ligands of the tumor necrosis factor family: A Sanhedrin verdict, Curr Opin Immunol," Vol.10, pp.279-288, 1998. https://doi.org/10.1016/S0952-7915(98)80166-0
  8. F. Mollinedo, R. Lopez-Perez, and C. Gajate, "Differential gene expression patterns coupled to commitment and acquisition of phenotypic hallmarks during neutrophil differentiation of human leukamia HL-60 cells," Gene, Vol.419, pp.16-26, 2008. https://doi.org/10.1016/j.gene.2008.04.015
  9. A. G. Porter, "Flipping thesafely caatch of procaspase-3,"Nature Chemical biology, Vol.2, pp.509-510, 2006. https://doi.org/10.1038/nchembio1006-509
  10. N. Parameswaran and S. Patial, "Tumor necrosis factor-${\alpha}$ signaling in Macrophages," Crit Rev Eukaryot Gene Expr, Vol.20, pp.87-103, 2010. https://doi.org/10.1615/CritRevEukarGeneExpr.v20.i2.10
  11. H. Hsu, J. Xiong, and D. V. Goeddel, "The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation," Cell, Vol.81, pp.495-504, 1995. https://doi.org/10.1016/0092-8674(95)90070-5
  12. H. Hsu, J. Huang, H. B. Shu, V. Baichwal, and D. V. Goeddel, "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex," Immunity, Vol.4, pp.387-396, 1996. https://doi.org/10.1016/S1074-7613(00)80252-6
  13. M. Takeuchi, M. Rothe, and D. V. Goeddel, "Anatomy of TRAF2.Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins," J Biol Chem, Vol.16, pp.19935-1994, 1996.
  14. M. S. Hayden and S. Ghosh, "Signaling to NF-kappaB pathway," Genes Dev., Vol.18, pp.2195-222, 2004. https://doi.org/10.1101/gad.1228704
  15. S. Vallabhapurapu and M. Karin, "Regulation and function of NF-kappaB transcription factors in the immune system," Annu Rev Immunol, Vol.27, pp.693-733, 2009. https://doi.org/10.1146/annurev.immunol.021908.132641
  16. L. A. Tartaglia, R. F. Weber, I. S. Figari, C. Reynolds, M. A. Jr Palladino, and D. V. Goeddel, "The two different receptors for tumor necrosis factor mediate distinct cellular responses," Proc Natl Acad Sci USA. Vol.88, pp.9292-9296, 1991. https://doi.org/10.1073/pnas.88.20.9292