Open Access

Rocaglamide overcomes tumor necrosis factor‑related apoptosis‑inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase‑8 through cellular FLICE‑like‑inhibitory protein downregulation

  • Authors:
    • Zhou Luan
    • Ying He
    • Fan He
    • Zhishui Chen
  • View Affiliations

  • Published online on: October 21, 2014     https://doi.org/10.3892/mmr.2014.2718
  • Pages: 203-211
  • Copyright: © Luan et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The enhancement of apoptosis is a therapeutic strategy used in the treatment of cancer. Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is a promising antitumor agent. However, hepatocellular carcinoma (HCC) cells exhibit marked resistance to the induction of cell death by TRAIL. The present study investigated whether rocaglamide, a naturally occurring product isolated from the genus Aglaia, is able to sensitize resistant HCC cells to TRAIL‑mediated apoptosis. Two HCC cell lines, HepG2 and Huh‑7, were treated with rocaglamide and/or TRAIL and the induction of apoptosis and effects on the TRAIL signaling pathway were investigated. The in vivo efficacy of rocaglamide was determined in TRAIL‑resistant Huh‑7‑derived tumor xenografts. Rocaglamide significantly sensitized the TRAIL‑resistant HCC cells to apoptosis by TRAIL, which resulted from the rocaglamide‑mediated downregulation of cellular FLICE‑like inhibitory protein and subsequent caspase‑8 activation. Furthermore, rocaglamide markedly inhibited tumor growth from Huh‑7 cells propagated in severe combined immunodeficient mice, suggesting that chemosentization also occurred in vivo. These data suggest that rocaglamide acted synergistically with TRAIL against the TRAIL‑resistant HCC cells. Thus, it is concluded that rocaglamide as an adjuvant to TRAIL‑based therapy may present a promising therapeutic approach for the treatment of HCC.
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January-2015
Volume 11 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Luan Z, He Y, He F and Chen Z: Rocaglamide overcomes tumor necrosis factor‑related apoptosis‑inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase‑8 through cellular FLICE‑like‑inhibitory protein downregulation. Mol Med Rep 11: 203-211, 2015
APA
Luan, Z., He, Y., He, F., & Chen, Z. (2015). Rocaglamide overcomes tumor necrosis factor‑related apoptosis‑inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase‑8 through cellular FLICE‑like‑inhibitory protein downregulation. Molecular Medicine Reports, 11, 203-211. https://doi.org/10.3892/mmr.2014.2718
MLA
Luan, Z., He, Y., He, F., Chen, Z."Rocaglamide overcomes tumor necrosis factor‑related apoptosis‑inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase‑8 through cellular FLICE‑like‑inhibitory protein downregulation". Molecular Medicine Reports 11.1 (2015): 203-211.
Chicago
Luan, Z., He, Y., He, F., Chen, Z."Rocaglamide overcomes tumor necrosis factor‑related apoptosis‑inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase‑8 through cellular FLICE‑like‑inhibitory protein downregulation". Molecular Medicine Reports 11, no. 1 (2015): 203-211. https://doi.org/10.3892/mmr.2014.2718