Advertisement

Science in China Series C: Life Sciences

, Volume 42, Issue 6, pp 635–643 | Cite as

Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa cells and protection by Bcl-2

  • Youping Deng
  • Chen Lin
  • Jie Zheng
  • Xiao Liang
  • Jieping Chen
  • Ming Fu
  • Peigen Xiao
  • Min Wu
Article

Abstract

It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of (As2O3) on human cervical cancer HeLa cells and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability assays, morphology alteration, flow cytometric analysis, DNA gel electrophoresis andin situ cell death detection (TUNEL), it was found that As2O3 inhibited the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed that As2O3 induced HeLa cell apoptosis possibly via decreasing the expression of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist As2O3 induced apoptosis, which might be relative to preventing the cells from As2O3 caused G2/M block, downregulation of c-myc gene expression and inhibition of viral gene expression was also noted. However, it was found that As2O3 at a high concentration could also induce apoptosis of HeLa cells overexpressing Bcl-2 possibly mainly via downregulating Bcl-2 expression and slightly inhibiting viral gene expression.

Keywords

arsenic trioxide (As2O3human cervical cancer cells apoptosis Bcl-2 overexpression 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sun, H. D., Ma, L., Hu, X. C. et al., Treatment of acute promyelocytic leukemia (32 cases) with intravenous arsenic triox-ide,Chin. J. Integr. Chin. West Med., 1992, 12: 170.Google Scholar
  2. 2.
    Zhang, P., Wang, S.Y., Hu, L.H. et al., Treatment of acute promyeliocytic leukemia (72 cases) with intravenous arsenic trioxide,Chin. J. Hematol., 1996, 17: 58.Google Scholar
  3. 3.
    Chen Guoqiang, Zhu Jun, Shi Xuegeng et al.,In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) induces NB4 cell apoptosis with downregulation of bcl-2 expression and modulation of PML-RAR2/PML proteins,Blood, 1996, 88(3): 1052.PubMedGoogle Scholar
  4. 4.
    Parkin, D.M., Laara, E., Muir, C.S., Estimates of the worldwide frequency of sixteen major cancer in 1980,Int. J. Can-cer, 1988, 41: 184.Google Scholar
  5. 5.
    Reed, J.C., Bcl-2 and the regulation of programmed cell death,J. Cell Biol., 1994, 124: 1.PubMedCrossRefGoogle Scholar
  6. 6.
    Fuhlbrigge, R. C., Fine, S. M., Unanue, E. R., Expression of membrane interleukin 1 by fibroblasts transfected with murine pro-interleukin lα cDNA,Proc. Natl. Acad. Sci. USA, 1988, 85: 5649.PubMedCrossRefGoogle Scholar
  7. 7.
    Sambrook, J., Fritsch, E. F., Maniatis, T.,Molecular Cloning:A Laboratory Manual, New York: Cold Spring Harbor Lab-oratory Press, 1989, 970–974.Google Scholar
  8. 8.
    Vistica, D. T., Skehan, P., Scudiero D., Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production,Cancer Res., 1991, 51: 2515.PubMedGoogle Scholar
  9. 9.
    Li, X. T., Lin, C., Li, P. Y. et al., The sensitivity of human gastric adenocarcinoma MGC803 to drugs and the clinical im-plication,Chin. J. Onco., 1989, 11(5): 332.Google Scholar
  10. 10.
    Nicoletti, I., Migliorati, G., Pagliacci, M.C. et al., A rapid and simple method for measuring thymocyte apoptosis by pro-pidium iodide staining and flow cytometry,J. Immunol. Methods, 1991, 139: 271.PubMedCrossRefGoogle Scholar
  11. 11.
    Hermann, M., Lorenz, H. M., Voll, R. et al., A rapid and simple method for the isolation of apoptotic DNA fragments,Nuclic. Acid Research, 1994, 22(24): 5506.CrossRefGoogle Scholar
  12. 12.
    Allouche, M., Bettaib, A., Vindis, C. et al., Influence of Bcl-2 overexpression on the ceramide pathway in daunorubin in-duced apoptosis of leukemic cells,Oncogene, 1997, 14: 1837.PubMedCrossRefGoogle Scholar
  13. 13.
    Kondo, S., Yin, D.L., Morimura, T. et al., Transfection with a bcl-2 expression vector protects transplanted bone marrow from chemotherapy induced myelosuppression,Cancer Res., 1994, 54: 2928.PubMedGoogle Scholar
  14. 14.
    Dwmarcq, C., Bunch, R.T., Creswell, D. et al., The role of cell cycle progression in cisplatin-induced apoptosis in Chinese hamster ovary cells,Cell Growth Differ., 1994, 5: 983.Google Scholar
  15. 15.
    Kangas, A., Nicholson, D. W., Holtta, E., Involvement of CPP32/caspase-3 in c-myc induced apoptosis,Oncogene, 1998, 16: 387.PubMedCrossRefGoogle Scholar
  16. 16.
    Lock, R.B., Thompson, B.S., Sullivan, D.M. et al., Potentiation of etoposide induced apoptosis by staurosporine in human tumor cells is associated with events downstream of DNA-protein complex formation,Cancer Chemother. Pharmacol., 1997, 39(5): 399.PubMedCrossRefGoogle Scholar
  17. 17.
    Magal, S. S., Jackman, A., Pei, X. F. et al., Induction of apoptosis in human keratinocytes containing mutated p53 alleles and inhibition by both the E6 and E7 oncoproteins,Int. J. Cancer, 1998, 75: 96.PubMedCrossRefGoogle Scholar

Copyright information

© Science in China Press 1999

Authors and Affiliations

  • Youping Deng
    • 1
  • Chen Lin
    • 1
  • Jie Zheng
    • 1
  • Xiao Liang
    • 1
  • Jieping Chen
    • 1
  • Ming Fu
    • 1
  • Peigen Xiao
    • 1
  • Min Wu
    • 1
  1. 1.State Key Laboratory of Molecular Oncology, Department of Cell Biology, Cancer InstituteChinese Academy of Medical Sciences, Peking Union Medical CollegeBeijingChina

Personalised recommendations