Journal of Acupuncture Research

Korean Acupuncture & Moxibustion Medicine Society (대한침구의학회)
권호 표지

Bee Venom Inhibits DU-145 Human Prostate Cancer Cell Growth Through Inactivation of NF-${\kappa}$B

Bee Venom이 NF-${\kappa}$B의 불활성화를 통해 DU-145 전립선 암세포의 성장에 미치는 영향

  • Shin, Jung-Mi (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyungwon University) ;
  • Song, Ho-Sueb (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyungwon University)
  • 신정미 (경원대학교 한의과대학 침구학교실) ;
  • 송호섭 (경원대학교 한의과대학 침구학교실)
  • Received : 2011.06.01
  • Accepted : 2011.06.13
  • Published : 2011.06.20
Download PDF
⟨ Previous Next ⟩

Abstract

목적 : 이 연구는 봉독이 NF-${\kappa}$B의 활성억제를 통하여 전립선 암세포주인 DU-145 세포의 성장을 억제하 는지를 확인하고 그 기전을 살펴보고자 하였다. 방법 : 봉독을 처리한 후 DU-145의 성장억제를 관찰하기 위해 WST-1 assay를 시행하였고, 세포자멸사의 관찰에는 DAPI staining assay를 통한 세포형태관찰을 시행하였으며, 염증관련유전자 발현 관찰에는 western blot analysis를 시행하였고, 세포자멸사와 연관된 NF-${\kappa}$B의 활성 변화를 관찰하기 위해 EMSA와 luciferase assay를 시행하였으며, DU-145에서 봉독과 NF-${\kappa}$B의 상호작용을 관찰하기 위해 transient transfection assay를 시행하여 세포생존율과 NF-${\kappa}$B의 활성 변동을 측정하였다. 결과 : DU-145 세포에서 봉독을 처리한 후 세포성장이 억제되었으며, 염증관련유전자 발현 및 NF-${\kappa}$B의 활성의 유의한 감소를 나타내었다. DU-145 세포에서 NF-${\kappa}$B의 p50와 IKK들을 치환하여 작용기를 없애고 봉독을 처리하였을 경우에도 세포활성 및 NF-${\kappa}$B의 활성의 유의한 감소를 나타내었다. 결론 : 이상의 결과는 봉독이 NF-${\kappa}$B의 활성 억제를 통하여 인간 전립선암세포주인 DU-145의 세포자멸사를 유발함으로써 증식억제 효과가 있음을 입증한 것으로 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 도움이 될 것으로 기대된다. 다만 그 기전에서 봉독은 기존연구와 같은 NF-${\kappa}$B p50 및 IKK들의 작용기와 상호작용 이외에 다른 기전이 관여되는 것으로 심화 연구를 요한다.

Keywords

References

  1. Hellerstedt BA, Pienta KJ. The current state of hormonal therapy for prostate cancer. CA Cancer J Clin. 2002 : 52, 154-79. https://doi.org/10.3322/canjclin.52.3.154
  2. Luciana D. Apoptosis induction in DU-145 human prostate carcinoma cells. Tissue and Cell. 2005 : 37, 379-84. https://doi.org/10.1016/j.tice.2005.06.006
  3. Timme TL, Satoh T, Tahir SA, Wang H, The BS, Butler EB, Miles BJ, Amato RJ, Kadmon D, Thompson TC. Therapeutic targets for metastatic prostate cancer. Curr Drug Targets. 4. 2003 : 251-61. https://doi.org/10.2174/1389450033491127
  4. Santos AF, Huang H, Tindall DJ. The androgen receptor: a potential target for therapy of prostate cancer. Steroids. 2004 : 69, 79-85. https://doi.org/10.1016/j.steroids.2003.10.005
  5. Srilatha S, Aruna VK, Donna MP, David F. Genistein potentiates the growth inhibitory effects of 1, 25-dihydroxyvitamin D3 in DU145 human prostate cancer cells: Role of the direct inhibition of CYP24 enzyme activity. Molecular and Cellular Endocrinology 241. 2005 : 49-61. https://doi.org/10.1016/j.mce.2005.05.001
  6. Brown RL, Haley TL, West KA, Crabb JW. Pseudechetoxin: a peptide blocker of cyclic nucleotide-gated ion channels. Proc Natl Acad Sci USA. 1999 ; 96 : 7549.
  7. Sher E, Giovannini F, Boot J, Lang B. Peptide neurotoxins, small-celllung carcinoma andneurological paraneoplastic syndromes. Biochimie. 2000 ; 82 : 92736.
  8. Van Lunteren E, Moyer M. Peptide toxin blockers of voltage-sensitive K+ channels: Inotropic effects on diaphragm. J Appl Physiol. 1999 ; 3 : 100916.
  9. Park HJ, Lee SH, Son DJ, Oh KW, Kim KH, Song HS, Kim GJ, Oh GT, Yoon DY and Hong JT. Antiarthritic effect of BV: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit. Arthritis Rheum. 2004 ; 50 : 3504-15. https://doi.org/10.1002/art.20626
  10. Holle L, Song W, Holle E, Wei Y, Wagner T, Yu X. A matrix metalloproteinase 2 cleavable melittin/avidin conjugate specifically targets tumor cells in vitro and in vivo. Int J Oncol. 2003 : 22, 93-8.
  11. Park HJ, Lee YK, Song HS, Kim KJ, Son DJ, Lee JW and Hong JT. Melittin inhibits human prostate cancer cell growth through induction of apoptotic cell death. J Toxicol Pub Health. 2006 ; 22(1) : 31-7.
  12. HS Lee, HS Song. BV inhibits LNCaP cell proliferation through induction of apoptosis via inactivation of NF-$\kappa$B. Journal of Acupuncture and Moxibustion. 2007 ; 25(2) : 59-74.
  13. HJ Oh, HS Song. BV inhibits PC-3 cell proliferation through induction of apoptosis via inactivation of NF-$\kappa$B. Journal of Acupuncture and Moxibustion. 2010 ; 27(3) : 1-14.
  14. DJ Son, MH Park, SJ Chae et al. Inhibitory effect of snake venom toxin from Vipera lebetina turanica on hormone-refractory human prostate cancer cell growth: induction of apoptosis through inactivation of nuclear factor KB. Mol Cancer Ther. 2007 ; 6(2) : 675-83. https://doi.org/10.1158/1535-7163.MCT-06-0328
  15. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis. 2000 ; 21 : 48595.
  16. Guseva NV, Taghiyev AF, Rokhlin OW, Cohen MB. Death receptor-induced cell death in prostate cancer. J Cell Biochem. 2004 ; 91 : 7099.
  17. Gurumurthy S, Vasudevan KM, Rangnekar VM. Regulation of apoptosis in prostate cancer. Cancer Metastasis Rev. 2001 ; 20 : 22543.
  18. Kantoff PW. New agents in the therapy of hormone-refractory patients with prostate cancer. Semin Oncol. 1995 ; 22(1) : 324.
  19. Suh J, Payvandi F, Edelstein LC et al. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells. Prostate. 2002 ; 52 : 183200.
  20. Raj GV, Sekula JA, Guo R, Madden JF, Daaka Y. Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-$\kappa$B. Prostate. 2004 ; 61 : 10513.
  21. Anton S, Andrew VS, Jozsef LV, Marta Z, Ren-Zhi C, Benjamin B, Brian D. Hammann, Patricia Armatis, Celia A. Kanashiro.Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling. European Journal of Cancer 41. 2005 : 2735-44. https://doi.org/10.1016/j.ejca.2005.08.022
  22. Kushlani G, Darrell KM, Richard ES, DDS AW. Inhibition of nuclear factor B induces apoptosis following treatment with tumor necrosis factor and an antioxidant in human prostate cancer cells. Cancer Detection and Prevention 26. 2002 : 229-37. https://doi.org/10.1016/S0361-090X(02)00061-2