Gambogic acid induces apoptosis and sensitizes TRAIL-mediated apoptosis through downregulation of cFLIPL in renal carcinoma Caki cells

  • Authors:
    • Ji Hoon Jang
    • Joo-Young Kim
    • Eon-Gi Sung
    • Eun-Ae Kim
    • Tae-Jin Lee
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  • Published online on: November 18, 2015     https://doi.org/10.3892/ijo.2015.3249
  • Pages: 376-384
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Abstract

Gambogic acid (GA) is a natural compound derived from brownish gamboge resin that shows a range of bioactivity, such as antitumor and antimicrobial properties. Although, GA is already known to induce cell death in a variety of cancer cells, the molecular basis for GA-induced cell death in renal cancer cells is unclear. In this study, a treatment with GA induced cell death in human renal carcinoma Caki cells in a dose-dependent manner. Treatment of Caki cells with GA decreased the levels of antiapoptotic proteins, such as Bcl-2 and XIAP in a dose-dependent manner. In addition, GA decreased the expression of the cFLIPL protein, which was downregulated at the transcriptional level without any change in the levels of cFLIPs expression. z-VAD (pan-caspase inhibitor) partially blocked GA-mediated cell death. GA-induced apoptotic cell death in Caki cells is mediated partly by the AIF translocation from the mitochondria into the nucleus via a caspase-independent pathway. In contrast, N-acetylcysteine (NAC), a ROS scavenger, had no effect on GA-induced cell death. The restoration of cFLIPL attenuated GA-induced cell death in Caki cells. Furthermore, a sub-toxic dose of GA sensitized TRAIL-mediated apoptosis in Caki cells. Pretreatment with z-VAD completely blocked GA plus TRAIL-mediated apoptosis. On the contrary, pretreatment with NAC partially inhibited GA plus TRAIL-induced apoptosis. Our findings suggested that GA induces apoptosis via the downregulation of cFLIPL and sensitized TRAIL-mediated apoptosis in Caki cells.
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January-2016
Volume 48 Issue 1

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Spandidos Publications style
Jang JH, Kim J, Sung E, Kim E and Lee T: Gambogic acid induces apoptosis and sensitizes TRAIL-mediated apoptosis through downregulation of cFLIPL in renal carcinoma Caki cells. Int J Oncol 48: 376-384, 2016.
APA
Jang, J.H., Kim, J., Sung, E., Kim, E., & Lee, T. (2016). Gambogic acid induces apoptosis and sensitizes TRAIL-mediated apoptosis through downregulation of cFLIPL in renal carcinoma Caki cells. International Journal of Oncology, 48, 376-384. https://doi.org/10.3892/ijo.2015.3249
MLA
Jang, J. H., Kim, J., Sung, E., Kim, E., Lee, T."Gambogic acid induces apoptosis and sensitizes TRAIL-mediated apoptosis through downregulation of cFLIPL in renal carcinoma Caki cells". International Journal of Oncology 48.1 (2016): 376-384.
Chicago
Jang, J. H., Kim, J., Sung, E., Kim, E., Lee, T."Gambogic acid induces apoptosis and sensitizes TRAIL-mediated apoptosis through downregulation of cFLIPL in renal carcinoma Caki cells". International Journal of Oncology 48, no. 1 (2016): 376-384. https://doi.org/10.3892/ijo.2015.3249