Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction

  • Authors:
    • Hak-Ryul Kim
    • Eun-Jung Kim
    • Sei-Hoon Yang
    • Eun-Taik Jeong
    • Channy Park
    • Se-Jin Kim
    • Myung-Ja Youn
    • Hong-Seob So
    • Raekil Park
  • View Affiliations

  • Published online on: June 1, 2006     https://doi.org/10.3892/ijo.28.6.1401
  • Pages: 1401-1408
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Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to enhance the responsiveness of tumor cells toward chemotherapeutic drugs and radiation. However, the precise mechanism of synergistic enhancement in tumoricidal activity is not clearly known. Herein, we demonstrate that the combination treatment of arsenic trioxide (As2O3) and sulindac resulted in a synergistic augmentation of cytotoxicity toward NCI-H157 lung cancer cells, which was revealed as apoptosis accompanied by chromatin fragmentation and an increase in sub-G0/G1 fraction. In addition, combination treatment with As2O3 and sulindac increased the catalytic activity of caspase-3, -8, and -9 along with induction of Fas/FasL expression and cytosolic release of cytochrome c. Pharmacologic scavenging study of reactive oxygen species (ROS) revealed that synergistic augmentation of cytotoxicity was achieved by generation of ROS, which might modulate the expression of Bcl-2 family proteins, the activity of caspase-3, and mitochondrial membrane potential transition.

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June 2006
Volume 28 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kim H, Kim E, Yang S, Jeong E, Park C, Kim S, Youn M, So H and Park R: Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction. Int J Oncol 28: 1401-1408, 2006
APA
Kim, H., Kim, E., Yang, S., Jeong, E., Park, C., Kim, S. ... Park, R. (2006). Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction. International Journal of Oncology, 28, 1401-1408. https://doi.org/10.3892/ijo.28.6.1401
MLA
Kim, H., Kim, E., Yang, S., Jeong, E., Park, C., Kim, S., Youn, M., So, H., Park, R."Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction". International Journal of Oncology 28.6 (2006): 1401-1408.
Chicago
Kim, H., Kim, E., Yang, S., Jeong, E., Park, C., Kim, S., Youn, M., So, H., Park, R."Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction". International Journal of Oncology 28, no. 6 (2006): 1401-1408. https://doi.org/10.3892/ijo.28.6.1401