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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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October 2013 Volume 43 Issue 4

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Article

CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells

  • Authors:
    • Eun Young Kim
    • Jae-Ha Ryu
    • An Keun Kim
  • View Affiliations / Copyright

    Affiliations: College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea
  • Pages: 1291-1300
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    Published online on: July 15, 2013
       https://doi.org/10.3892/ijo.2013.2018
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Abstract

Caffeic acid phenethyl ester (CAPE), a phenolic compound derived from honeybee propolis, has been reported to possess anticancer activities in several types of malignant cells. Here, we show that treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with CAPE significantly sensitized SK-Hep1 cells to TRAIL-induced apoptosis. The sensitization to TRAIL was accompanied by the activation of extrinsic and intrinsic apoptotic pathways, leading to the activation of caspases, mitochondrial disruption and PARP cleavage. Moreover, TRAIL receptors, such as DR4 and DR5 were significantly upregulated by CAPE treatment, and both DR4/Fc and DR5/Fc chimera markedly abrogated apoptosis induced by CAPE and TRAIL, demonstrating the critical role of these death receptors in combination-induced apoptosis. The effect of CAPE on mitogen-activated protein kinases (MAPKs) was further examined, where CAPE treatment resulted in the activation of p38 and the inhibition of JNK, without affecting levels of phospho-ERK. Our results showed that p38 and JNK exhibited the opposite role in SK-Hep1 cells. The inhibition of p38, using SB203580, blocked the CAPE-induced expression of death receptors and attenuated the combination‑induced apoptosis, suggesting the pro-apoptotic role of p38. In contrast, JNK-specific inhibition, by SP600125, triggered upregulation of DR4 and DR5, and sensitized SK-Hep1 cells to TRAIL, indicating that the CAPE-induced suppression of JNK may contribute to the sensitizing effect of CAPE through the upregulation of death receptors. Taken together, these results indicate that CAPE potentiated TRAIL-induced apoptosis in SK-Hep1 cells, through upregulation of TRAIL receptors via modulation of p38 and JNK signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Kim EY, Ryu J and Kim AK: CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells. Int J Oncol 43: 1291-1300, 2013.
APA
Kim, E.Y., Ryu, J., & Kim, A.K. (2013). CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells. International Journal of Oncology, 43, 1291-1300. https://doi.org/10.3892/ijo.2013.2018
MLA
Kim, E. Y., Ryu, J., Kim, A. K."CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells". International Journal of Oncology 43.4 (2013): 1291-1300.
Chicago
Kim, E. Y., Ryu, J., Kim, A. K."CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells". International Journal of Oncology 43, no. 4 (2013): 1291-1300. https://doi.org/10.3892/ijo.2013.2018
Copy and paste a formatted citation
x
Spandidos Publications style
Kim EY, Ryu J and Kim AK: CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells. Int J Oncol 43: 1291-1300, 2013.
APA
Kim, E.Y., Ryu, J., & Kim, A.K. (2013). CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells. International Journal of Oncology, 43, 1291-1300. https://doi.org/10.3892/ijo.2013.2018
MLA
Kim, E. Y., Ryu, J., Kim, A. K."CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells". International Journal of Oncology 43.4 (2013): 1291-1300.
Chicago
Kim, E. Y., Ryu, J., Kim, A. K."CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma cells". International Journal of Oncology 43, no. 4 (2013): 1291-1300. https://doi.org/10.3892/ijo.2013.2018
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