Effects of Arsenic Compounds $(AS_2O_3\;and\;AS_4O_6)$ on the Induction of Apoptotic Cell Death in A549 Human Non-small Cell Lung Cancer Cells

비소화합물에 의한 A549 폐암세포의 증식억제에 관한 연구

  • Choi, Yung-Hyun (Department of Biochemistry Research Institute of Oriental Medicine Dongeui University College of Oriental Medicine) ;
  • Choi, Woo-Young (Department of Biochemistry Research Institute of Oriental Medicine Dongeui University College of Oriental Medicine) ;
  • Choi, Byung-Tae (Department of Anatomy, Dongeui University College of Oriental Medicine) ;
  • Lee, Yong-Tae (Department of Physilogy, Dongeui Univesity College of Oriental Medicine) ;
  • Lee, Won-Ho (Department of Biology, Pusan National University)
  • 최영현 (동의대학교 한의과대학 생화학교실 및 한의학연구소) ;
  • 최우영 (동의대학교 한의과대학 생화학교실 및 한의학연구소) ;
  • 최병태 (동의대학교 한의과대학 해부학교실) ;
  • 이용태 (동의대학교 한의과대학 생리학교실) ;
  • 이원호 (부산대학교 자연과학대학 생물학과)
  • Published : 2005.08.01

Abstract

Recently, arsenic compounds were considered as novel agents for treatment of acute promyelocytic leukemia and malignant tumors. However, it showed severe toxicity effect on normal tissue at the same time. In this study, to investigate the possible molecular mechanism (s) of arsenic compounds as candidate of anti-cancer drugs, we compared the abilities of two arsenic compounds, tetraarsenic oxide $(AS_4O_6)$ and arsenic trioxide (diarsenic oxide, $As_2O_3$), to induce cell growth inhibition as well as apoptosis induction in A549 human non-small cell lung cancer cells. Both $As_4O_6\;and\;As_2O_3$ treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of G1 arrest of the cell cycle and apoptotic cell death. However, $As_4O_6$ induced growth inhibition and apoptosis in A549 cells at much lower concentrations than $As_2O_3.\;As_4O_6$ down-regulated the levels of anti-apoptotic Bcl-2 protein, however, the levels of Bax, a pro-apoptotic protein, were up-regulated in a dose-dependent manner. In conclusion, $As_4O_6$ might be a new arsenic compound which may induce apoptosis in A549 cells by modulation the Bcl-2 family and deserves further evaluation.

Keywords

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