Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1-dependent pathways

  • Authors:
    • Pornthip Waiwut
    • Akiko Inujima
    • Hiroki Inoue
    • Ikuo Saiki
    • Hiroaki Sakurai
  • View Affiliations

  • Published online on: September 1, 2011     https://doi.org/10.3892/ijo.2011.1182
  • Pages: 203-208
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Abstract

Tumor necrosis factor-alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) are apoptosis-inducing ligands that stimulate death receptors. In this study, we investigated the effects of bufotalin, a major compound in toad venom, on sensitizing TNF-α and TRAIL-induced apoptosis of HeLa cells. Bufotalin promoted death receptor-mediated cell death, especially TRAIL-induced apoptosis, through activation of caspase-3 and PARP-1. Mitochondrial Bid-dependent pathway was activated in TNF-α-induced cell death. Cotreatment of bufotalin with TRAIL resulted in the downregulation of anti-apoptotic proteins, including Bcl-XL, Mcl-1, survivin and XIAP, and the up-regulation of MAPKs and TRAIL receptor DR5. In addition, phosphorylation of STAT1 was strongly inhibited by bufotalin. Moreover, DR5 expression was induced by knocking down the STAT1 expression. Moreover, the TRAIL-induced apoptotic response was promoted by STAT1 siRNA. Our results demonstrated that bufotalin is a powerful sensitizer of death receptor-induced apoptosis in cancer cells.

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January 2012
Volume 40 Issue 1

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Spandidos Publications style
Waiwut P, Inujima A, Inoue H, Saiki I and Sakurai H: Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1-dependent pathways. Int J Oncol 40: 203-208, 2012
APA
Waiwut, P., Inujima, A., Inoue, H., Saiki, I., & Sakurai, H. (2012). Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1-dependent pathways. International Journal of Oncology, 40, 203-208. https://doi.org/10.3892/ijo.2011.1182
MLA
Waiwut, P., Inujima, A., Inoue, H., Saiki, I., Sakurai, H."Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1-dependent pathways". International Journal of Oncology 40.1 (2012): 203-208.
Chicago
Waiwut, P., Inujima, A., Inoue, H., Saiki, I., Sakurai, H."Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1-dependent pathways". International Journal of Oncology 40, no. 1 (2012): 203-208. https://doi.org/10.3892/ijo.2011.1182