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Article

Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells

  • Authors:
    • Jeong-Seok Park
    • Dong Yeok Shin
    • Yeon-Weol Lee
    • Chong-Kwan Cho
    • Gi Young Kim
    • Wun-Jae Kim
    • Hwa-Seung Yoo
    • Yung Hyun Choi
  • View Affiliations / Copyright

    Affiliations: Department of East-West Cancer Center, College of Oriental Medicine, Daejeon University, Daejeon 301-724, Republic of Korea, Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea
  • Pages: 1210-1219
    |
    Published online on: December 20, 2011
       https://doi.org/10.3892/ijo.2011.1310
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Abstract

In the present study, the effects of the whole skin of Venenum bufonis on apoptotic and anti-invasive activity in A549 human lung cancer cells were investigated. Treatment with extract of the whole skin of V. bufonis (SVB) resulted in a significant decrease in cell growth of A549 cells, depending on dosage, which was associated with apoptosis induction, as proved by chromatin condensation and accumulation of apoptotic fraction. SVB treatment induced expression of death receptor-related proteins, such as death receptor 4, which further triggered activation of caspase-8 and cleavage of Bid. In addition, the increase in apoptosis by SVB treatment was correlated with dysfunction of mitochondria, activation of caspase-9 and -3, downregulation of IAP family proteins, such as XIAP, cIAP-1 and cIAP-2, and concomitant degradation of activated caspase-3-specific target proteins, such as poly (ADP-ribose) polymerase and β-catenin proteins. However, z-DEVD-fmk, a caspase-3-specific inhibitor, blocked SVB-induced apoptosis and increased the survival rate of SVB-treated cells, indicating that activation of caspase-3 plays a key role in SVB-induced apoptosis. In addition, within concentrations that were not cytotoxic to A549 cells, SVB induced marked inhibition of cell motility and invasiveness. Activities of matrix metalloproteinase (MMP)-2 and MMP-9 in AGS cells were dose-dependently inhibited by treatment with SVB, and this was also correlated with a decrease in expression of their mRNA and proteins, and upregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 mRNA expression. Further studies are needed; however, the results indicated that SVB induces apoptosis of A549 cells through a signaling cascade of death receptor-mediated extrinsic as well as mitochondria-mediated intrinsic caspase pathways. Our data also demonstrated that MMPs are critical targets of SVB-induced anti-invasiveness in A549 cells.
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Copy and paste a formatted citation
Spandidos Publications style
Park J, Shin DY, Lee Y, Cho C, Kim GY, Kim W, Yoo H and Choi YH: Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells. Int J Oncol 40: 1210-1219, 2012.
APA
Park, J., Shin, D.Y., Lee, Y., Cho, C., Kim, G.Y., Kim, W. ... Choi, Y.H. (2012). Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells. International Journal of Oncology, 40, 1210-1219. https://doi.org/10.3892/ijo.2011.1310
MLA
Park, J., Shin, D. Y., Lee, Y., Cho, C., Kim, G. Y., Kim, W., Yoo, H., Choi, Y. H."Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells". International Journal of Oncology 40.4 (2012): 1210-1219.
Chicago
Park, J., Shin, D. Y., Lee, Y., Cho, C., Kim, G. Y., Kim, W., Yoo, H., Choi, Y. H."Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells". International Journal of Oncology 40, no. 4 (2012): 1210-1219. https://doi.org/10.3892/ijo.2011.1310
Copy and paste a formatted citation
x
Spandidos Publications style
Park J, Shin DY, Lee Y, Cho C, Kim GY, Kim W, Yoo H and Choi YH: Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells. Int J Oncol 40: 1210-1219, 2012.
APA
Park, J., Shin, D.Y., Lee, Y., Cho, C., Kim, G.Y., Kim, W. ... Choi, Y.H. (2012). Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells. International Journal of Oncology, 40, 1210-1219. https://doi.org/10.3892/ijo.2011.1310
MLA
Park, J., Shin, D. Y., Lee, Y., Cho, C., Kim, G. Y., Kim, W., Yoo, H., Choi, Y. H."Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells". International Journal of Oncology 40.4 (2012): 1210-1219.
Chicago
Park, J., Shin, D. Y., Lee, Y., Cho, C., Kim, G. Y., Kim, W., Yoo, H., Choi, Y. H."Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells". International Journal of Oncology 40, no. 4 (2012): 1210-1219. https://doi.org/10.3892/ijo.2011.1310
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