Differential effects of resveratrol and novel resveratrol derivative, HS-1793, on endoplasmic reticulum stress-mediated apoptosis and Akt inactivation

  • Authors:
    • Hee Jung Um
    • Jae Hoon Bae
    • Jong-Wook Park
    • Hongsuk Suh
    • Na Young Jeong
    • Young Hyun Yoo
    • Taeg Kyu Kwon
  • View Affiliations

  • Published online on: April 1, 2010     https://doi.org/10.3892/ijo_00000581
  • Pages: 1007-1013
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Abstract

Since resveratrol (3,4',5 tri-hydroxystilbene), which has been shown to inhibit multistage carcinogenesis, is not a potent cytotoxic compound, several studies were undertaken to obtain synthetic analogues of resveratrol with potent activity. We previously reported that a resveratrol derivative HS-1793 exhibits stronger antitumor effects than resveratrol in several cancer cell types. The present study was undertaken to reveal precise mechanism by which HS-1793 induces cell death. The induction of CCAAT/enhancer-binding protein-homologous protein (CHOP) and glucose-regulated protein (GRP)-78, and ER stress-specific XBP1 splicing were found in HT29 human colon carcinoma cells treated with resveratrol. Conversely, these manifestations were not observed in HT29 cells treated with HS-1793. Inhibition of caspase-4 activity by z-LEVD-fmk significantly reduced the induction of apoptosis by resveratrol but not by HS-1793. These findings suggest that HS-1793, contrary to resveratrol, does not induce ER stress-mediated apoptosis. Importantly, we observed that HS-1793 but not resveratrol decreased phosphorylated Akt level. We also demonstrated that HS-1793, compared to resveratrol, exerted more effective apoptosis inducing activity in Akt-activated cells. Taken together, the stronger antitumor activity of HS-1793 originates, at least in part, from its ability for Akt inactivation.

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April 2010
Volume 36 Issue 4

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

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Spandidos Publications style
Um HJ, Bae JH, Park J, Suh H, Jeong NY, Yoo YH and Kwon TK: Differential effects of resveratrol and novel resveratrol derivative, HS-1793, on endoplasmic reticulum stress-mediated apoptosis and Akt inactivation. Int J Oncol 36: 1007-1013, 2010.
APA
Um, H.J., Bae, J.H., Park, J., Suh, H., Jeong, N.Y., Yoo, Y.H., & Kwon, T.K. (2010). Differential effects of resveratrol and novel resveratrol derivative, HS-1793, on endoplasmic reticulum stress-mediated apoptosis and Akt inactivation. International Journal of Oncology, 36, 1007-1013. https://doi.org/10.3892/ijo_00000581
MLA
Um, H. J., Bae, J. H., Park, J., Suh, H., Jeong, N. Y., Yoo, Y. H., Kwon, T. K."Differential effects of resveratrol and novel resveratrol derivative, HS-1793, on endoplasmic reticulum stress-mediated apoptosis and Akt inactivation". International Journal of Oncology 36.4 (2010): 1007-1013.
Chicago
Um, H. J., Bae, J. H., Park, J., Suh, H., Jeong, N. Y., Yoo, Y. H., Kwon, T. K."Differential effects of resveratrol and novel resveratrol derivative, HS-1793, on endoplasmic reticulum stress-mediated apoptosis and Akt inactivation". International Journal of Oncology 36, no. 4 (2010): 1007-1013. https://doi.org/10.3892/ijo_00000581