The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells

  • Authors:
    • Xuexin Zhang
    • Wanhai Xu
    • Jun Su
    • Ming Chu
    • Hua Jin
    • Guofu Li
    • Chunlei Tan
    • Xin Wang
    • Chao Wang
  • View Affiliations

  • Published online on: February 17, 2014     https://doi.org/10.3892/ijmm.2014.1660
  • Pages: 987-993
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

In a previous study, we reported that resveratrol exerts antitumor effects through the estrogen receptor in prolactinoma. The autophagy/lysosomal degradation pathway plays an important role in damage control and energy efficiency. In this study, we investigated the involvement of autophagy and the related signaling pathways in resveratrol-induced apoptosis of GH3 cells. We demonstrate that resveratrol inhibits cell proliferation and induces apoptosis in a dose-dependent manner in GH3 cells. The cleavage of PARP was also observed, and the activation of caspase-3 and caspase-8 was detected. Consistent with this finding, the inhibition of caspase activation effectively attenuated resveratrol-induced cell apoptosis. In addition, the decreased level of Bcl-2 was also observed. The induction of autophagy was confirmed by the detection of the formation of autophagic vacuoles, and the increase in microtubule-associated protein 1 light chain 3 (LC3)-II and beclin-1 levels, two hallmarks of autophagy. Pre-treatment with bafilomycin A1 or 3-methyladenine, inhibitors of autophagy, enhanced the resveratrol-mediated caspase activation and cell death. Moreover, resveratrol induced the activation of ERK1/2, as well as the downregulation of Akt and mTOR phosphorylation. Taken together, these findings indicate that resveratrol induces caspase-dependent apoptosis and decreases Bcl-2 levels. In addition, resveratrol-induced autophagy is regulated by the PI3K/Akt/mTOR and ERK1/2 pathways. Furthermore, the inhibition of autophagy increases the cytotoxicity of resveratrol to GH3 cells.
View Figures
View References

Related Articles

Journal Cover

2014-April
Volume 33 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang X, Xu W, Su J, Chu M, Jin H, Li G, Tan C, Wang X and Wang C: The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells. Int J Mol Med 33: 987-993, 2014
APA
Zhang, X., Xu, W., Su, J., Chu, M., Jin, H., Li, G. ... Wang, C. (2014). The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells. International Journal of Molecular Medicine, 33, 987-993. https://doi.org/10.3892/ijmm.2014.1660
MLA
Zhang, X., Xu, W., Su, J., Chu, M., Jin, H., Li, G., Tan, C., Wang, X., Wang, C."The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells". International Journal of Molecular Medicine 33.4 (2014): 987-993.
Chicago
Zhang, X., Xu, W., Su, J., Chu, M., Jin, H., Li, G., Tan, C., Wang, X., Wang, C."The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells". International Journal of Molecular Medicine 33, no. 4 (2014): 987-993. https://doi.org/10.3892/ijmm.2014.1660