Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Induction of Apoptosis by Bee Venom in A549 Human Lung Epithelial Cancer Cells through Modulation of Bcl-2 and IAP Family and Activation of Caspases

Bcl-2 및 IAP family의 발현 변화와 caspase 활성을 통한 봉독의 인체폐암세포 apoptosis 유도

  • Woo, Hyun-Joo (Department of Oriental Medicine, Dong-Eui University College of Oriental Medicine) ;
  • Kim, Hyun-Joong (Department of Oriental Medicine, Dong-Eui University College of Oriental Medicine) ;
  • Hong, Su-Hyun (Department of Oriental Medicine, Dong-Eui University College of Oriental Medicine) ;
  • Hong, Sang-Hoon (Department of Oriental Medicine, Dong-Eui University College of Oriental Medicine) ;
  • Choi, Byung-Tae (Department of Anatomy, Pusan National University Graduate School of Oriental Medicine) ;
  • Lee, Yong-Tae (Department of Oriental Medicine, Dong-Eui University College of Oriental Medicine) ;
  • Park, Dong-Il (Department of Oriental Medicine, Dong-Eui University College of Oriental Medicine) ;
  • Choi, Yung-Hyun (Department of Oriental Medicine, Dong-Eui University College of Oriental Medicine)
  • 우현주 (동의대학교 한의과대학 한의학과) ;
  • 김현중 (동의대학교 한의과대학 한의학과) ;
  • 홍수현 (동의대학교 한의과대학 한의학과) ;
  • 홍상훈 (동의대학교 한의과대학 한의학과) ;
  • 최병태 (부산대학교 한의학전문대학원) ;
  • 이용태 (동의대학교 한의과대학 한의학과) ;
  • 박동일 (동의대학교 한의과대학 한의학과) ;
  • 최영현 (동의대학교 한의과대학 한의학과)
  • Published : 2007.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Bee venom is used to treat inflammatory diseases in Korean traditional medicine and has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in bee venom-induced apoptosis are still uncharacterized in human lung cancer cells. In the present study, we investigated the effects of bee venom on the apoptosis of A549 human lung epithelial cancer cells. Treatment of bee venom inhibited the cell viability and induced apoptosis in a concentration-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. Bee venom-induced apoptosis in A549 cells was associated with a marked inhibition of anti-apoptotic Bcl-2 expression without significant changes in the levels of Bax and Bcl-xL. Bee venom treatment also inhibited the levels of IAP family members such as cIAP-1 and cIAP-2 and induced the proteolytic activation of caspase-3 and caspase-9. Although further studies are needed, the present results suggest that apoptotic signals evoked by bee vemon in A549 cancer cells may converge caspases activation through a down-regulation of Bcl-2 rather than an up-regulation of Bax. These findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of bee vemon in human cancer cells.

본 연구에서 봉독의 apoptosis 유도에 의한 항암기전 효능을 A549 인체폐암세포를 대상으로 조사하였으며, apoptosis 유발에 관여할 것으로 예상되는 중요한 유전자들의 발현 및 활성에 미치는 봉독의 영향을 조사하였다. A549 세포의 생존율은 봉독의 처리 농도 증가에 따라 강력하게 억제되었으며, 이는 염색질 응축 현상을 동반한 apoptosis 유발에 의한 것임을 알 수 있었다. 봉독 처리에 의한 apoptosis 유발은 Bax 및 Bcl-xL의 발현 변화 없이 Bcl-2의 발현 감소에 따른 상대적인 Bax의 발현 증가와 IAP family에 속하는 인자들의 발현 감소 및 caspase의 활성화와 연관성이 있었다.

Keywords

References

  1. Ahn, C. B., C. W. Im, H. M. Youn, S. J. Park and Y. H. Choi. 2003. Melittin-induced apoptosis is associated with inhibition of COX-2 and hTERT expression in human lung carcinoma A549 cells, J. Kor, Acupuncture Moxibustion Soc. 20, 93-106.
  2. Allen, R. T., M. W. Cluck and D. K. Agrawal. 1998. Mechanisms controlling cellular suicide: role of Bcl-2 and caspases. Cell Mol. Life Sci. 54, 427-445. https://doi.org/10.1007/s000180050171
  3. Assem, E. S. and G. Atkinson. 1973. Histamine release by MCDP (401), a peptide from the venom of the honey bee. Bri. Pharmacol. 48, 337-338.
  4. 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
  5. Evans, V. G. 1993. Multiple pathways to apoptosis. Cell Biol. Int. 17, 461-476. https://doi.org/10.1006/cbir.1993.1087
  6. Habermann, E. 1971. Chemistry, pharmacology and toxicology of bee, wasp and hornet venoms. In venomous animals and their venoms. pp. 3-61, Academic Press. New York.
  7. 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
  8. Kwon, D. H., J. D. Lee and D. Y. Choi. 2001. The study of anti-cancer effects of Bee venom for aqua-acupuncture. J. Kor. Acupuncture Moxibustion Soc. 18, 129-145.
  9. Kwon, K. R., H. K. Hoh and C. H. Kim. 1994. The study of the introduction of Bee venom acupuncture, biochemistry and pharmachology have been obtained the following results. J. Kor. Acupuncture Moxibustion Soc. 11, 159-171.
  10. Lee, J. H., J. D. Jin, S. W. Lee, S. W. Han, S. T. Kim and J. S. Shin. 2002. The effect of Bee Venom and melittin herbal acupuncture solution to apoptosis in NG pretreated neuroblastoma cell line. J. Kor. Acupuncture Moxibustion Soc. 19, 189-202.
  11. Moon, D. O., S. Y. Park, M. S. Heo, K. C. Kim, C. Park, W. S. Ko, Y. H. Choi and G. Y. Kim. 2006. Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. Int. Immunopharmacol. 6, 1796-1807. https://doi.org/10.1016/j.intimp.2006.07.027
  12. Park, D. I., J. H. Lee, S. K. Moon, C. H. Kim, Y. T. Lee, J. Cheong, B. T. Choi and Y. H. Choi. 2005. Induction of apoptosis and inhibition of telomerase activity by aqueous extract from Platycodon grandiflorum in human lung carcinoma cells. Pharmacol. Res. 51, 437-443. https://doi.org/10.1016/j.phrs.2004.11.003
  13. 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
  14. Saini, S. S., A. K. Chopra and J. W. Peterson. 1999. Melittin activates endogenous phospholipase D during cytolysis of human monocytic leukemia cells. Toxicon 37, 1605-1619. https://doi.org/10.1016/S0041-0101(99)00110-5
  15. Sakamoto, T., W. T. Repasky, K. Uchida, A. Hirata and F. Hirata. 1996. Modulation of cell death pathways to apoptosis and necrosis of H2O2-treated rat thymocytes by lipocortin I. Biochem. Biophys. Res. Commun. 220, 643-647. https://doi.org/10.1006/bbrc.1996.0457
  16. 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
  17. Spoerri, P. E. 1973. Apamin from bee venom. Neurobiology 3, 207-214.
  18. Vegran, F., R. Boidot, C. Oudin, J. M. Riedinger and S. Lizard-Nacol. 2005. Implication of alternative splice transcripts of caspase-3 and survivin in chemoresistance. Bull. Cancer 92, 219-26.
  19. Vento, R., N. D'Alessandro, M. Giuliano, M. Lauricella, M. Carabillo and G. Tesoriere. 2000. Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress. Exp. Eye Res. 70, 503-517. https://doi.org/10.1006/exer.1998.0810
  20. Woo, H. J., S. J. Lee, B. T. Choi, Y. M. Park and Y. H. Choi. 2007. Induction of apoptosis and inhibition of telomerase activity by trichostatin A, a histone deacetylase inhibitor, in human leukemic U937 cells. Exp. Mol. Pathol. 82, 77-84. https://doi.org/10.1016/j.yexmp.2006.02.004
  21. Yeo, S. W., S. J. Chul, Y. H. Choi and K. J. Jang. 2003. Induction of the growth inhibition and apoptosis by beevenom in human breast carcinoma MCF-7 cells. J. Kor. Acupuncture Moxibustion Soc. 20, 45-62.