Matrine-induced autophagy regulated by p53 through AMP-activated protein kinase in human hepatoma cells

  • Authors:
    • Shan-Bu Xie
    • Xing-Xing He
    • Shu-Kun Yao
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  • Published online on: May 28, 2015     https://doi.org/10.3892/ijo.2015.3023
  • Pages: 517-526
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Abstract

Matrine, one of the main extract components of Sophora flavescens, has been shown to exhibit inhibitory effects on some tumors through autophagy. However, the mechanism underlying the effect of matrine remains unclear. The cultured human hepatocellular carcinoma cell line HepG2 and SMMC‑7721 were treated with matrine. Signal transduction and gene expression profile were determined. Matrine stimulated autophagy in SMMC‑7721 cells in a mammalian target of rapamycin (mTOR)-dependent manner, but in an mTOR-independent manner in HepG2 cells. Next, in HepG2 cells, autophagy induced by matrine was regulated by p53 inactivation through AMP-activated protein kinase (AMPK) signaling transduction, then AMPK suppression switched autophagy to apoptosis. Furthermore, the interferon (IFN)-inducible genes, including interferon α-inducible protein 27 (IFI27) and interferon induced transmembrane protein 1 (IFITM1), which are downstream effector of p53, might be modulated by matrine-induced autophagy. In addition, we found that the p53 protein isoforms, p53β, p53γ, ∆133p53, and ∆133p53γ, due to alternative splicing of intron 9, might be regulated by the p53-mediated autophagy. These results show that matrine induces autophagy in human hepatoma cells through a novel mechanism, which is p53/AMPK signaling pathway involvement in matrine-promoted autophagy.
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August-2015
Volume 47 Issue 2

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

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Spandidos Publications style
Xie S, He X and Yao S: Matrine-induced autophagy regulated by p53 through AMP-activated protein kinase in human hepatoma cells. Int J Oncol 47: 517-526, 2015.
APA
Xie, S., He, X., & Yao, S. (2015). Matrine-induced autophagy regulated by p53 through AMP-activated protein kinase in human hepatoma cells. International Journal of Oncology, 47, 517-526. https://doi.org/10.3892/ijo.2015.3023
MLA
Xie, S., He, X., Yao, S."Matrine-induced autophagy regulated by p53 through AMP-activated protein kinase in human hepatoma cells". International Journal of Oncology 47.2 (2015): 517-526.
Chicago
Xie, S., He, X., Yao, S."Matrine-induced autophagy regulated by p53 through AMP-activated protein kinase in human hepatoma cells". International Journal of Oncology 47, no. 2 (2015): 517-526. https://doi.org/10.3892/ijo.2015.3023