TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells

  • Authors:
    • Xuan Zhang
    • Meilan Zhang
    • Bin Xiao
    • Wenjun Jiao
    • Silin Zhang
    • Xuewu Zhang
  • View Affiliations

  • Published online on: January 5, 2018     https://doi.org/10.3892/or.2018.6196
  • Pages: 1423-1431
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Abstract

TTF1‑NP is a flavonoid nanoparticle based on 5,2',4'‑trihydroxy‑6,7,5'‑trimethoxyflavone (TTF1), which is derived from the medicinal plant Sorbaria sorbifolia that grows in the Changbai Mountain. We previously demonstrated antitumor effects of TTF1‑NP in human hepatoma including induction of apoptosis and inhibition of angiogenesis, migration and invasion. Herein, we examined the effects of TTF1‑NP on autophagy and its relationship with apoptosis, and explored potential underlying mechanisms in human hepatoma cell lines. We conducted cell viability assays, Annexin V/propidium iodide double staining, Hoechst staining, monodansylcadaverine staining, transmission electron microscopy, green fluorescent protein‑light chain 3 plasmid transfection and western blots. We found that TTF1‑NP induced apoptosis and autophagy in HepG2 and SMMC‑7721 cells. Pretreatment with the autophagy inhibitor 3‑methyladenine promoted TTF1‑NP‑induced apoptosis. TTF1‑NP decreased levels of phosphorylated (p)‑Akt, p‑mTOR and p‑ERK1/2 and increased p‑JNK levels in the two cell lines. Treating cells with insulin, SP600125 and U0126 indicated that the Akt/mTOR pathway and JNK were involved in TTF1‑NP‑induced autophagy. Together, these findings suggest that TTF1‑NP induced protective apoptosis‑related autophagy by modulating the Akt/mTOR and JNK pathways in HepG2 and SMMC‑7721 cells. Therefore, autophagy may be a potential target for TTF1‑NP in human hepatoma therapy.
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March-2018
Volume 39 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang X, Zhang M, Xiao B, Jiao W, Zhang S and Zhang X: TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells. Oncol Rep 39: 1423-1431, 2018
APA
Zhang, X., Zhang, M., Xiao, B., Jiao, W., Zhang, S., & Zhang, X. (2018). TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells. Oncology Reports, 39, 1423-1431. https://doi.org/10.3892/or.2018.6196
MLA
Zhang, X., Zhang, M., Xiao, B., Jiao, W., Zhang, S., Zhang, X."TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells". Oncology Reports 39.3 (2018): 1423-1431.
Chicago
Zhang, X., Zhang, M., Xiao, B., Jiao, W., Zhang, S., Zhang, X."TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells". Oncology Reports 39, no. 3 (2018): 1423-1431. https://doi.org/10.3892/or.2018.6196