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Article

Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells

  • Authors:
    • Bo Kou
    • Wei Liu
    • Xu Xu
    • Yang Yang
    • Qiuyue Yi
    • Fengwei Guo
    • Jianpeng Li
    • Jinsong Zhou
    • Qingshan Kou
  • View Affiliations / Copyright

    Affiliations: Department of Cadiovascular Sugery, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Human Resources, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China, Medical Center, First People's Hospital of Xianyang, Xianyang, Shaanxi 712000, P.R. China
  • Pages: 3137-3143
    |
    Published online on: September 21, 2017
       https://doi.org/10.3892/or.2017.5988
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Abstract

Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy. Thus, we focused on the correlation between autophagy and apoptosis upon tetrandrine treatment in human bladder cancer cells. Firstly, our results observed a marked increase in autophagic double-membrane vacuoles and fluorescent puncta of red fluorescence protein-green fluorescence protein-LC3 (GRP-RFP-LC3) upon tetrandrine treatment, as evidenced by transmission electron microscopy and confocal fluorescence microscopy. Secondly, the expression of LC3-II was increased in tetrandrine-treated T24 and 5637 cells in a time- and concentration-dependent manner. Subsequently, downregulation of p62 and LC3 turnover assay further confirmed that tetrandrine induced autophagic flux in bladder cancer T24 and 5637 cells. Thirdly, the protein levels of phosphorylated-AMP-activated protein kinase (AMPK) and phosphorylated-acetyl-coenzyme A carboxylase (ACC) were upregulated in the tetrandrine-treated cells, while the mammalian target of rapamycin (mTOR)-related proteins were downregulated. Moreover, AICAR, a common AMPK activator, further increased the expression the LC3-II, while AMPK inhibitor compound C partially reversed the LC3-II protein levels in bladder cancer T24 cells. Finally, AICAR significantly reinforced the growth inhibition and apoptosis induction of tetrandrine in T24 and 5637 cells, while compound C had an opposite effect, suggesting that AMPK-mediated autophagy enhanced the cytotoxic and pro-apoptosis effect of tetrandrine in human bladder cancer cells. Taken together, the present study showed that tetrandrine induced autophagy in human bladder cancer cells by regulating the AMPK/mTOR signaling pathway, which contributed to the apoptosis induction by tetrandrine, indicating that tetrandrine may be a potential anticancer candidate for the treatment of bladder cancer, and autophagy may be a possible mechanism for cancer therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Kou B, Liu W, Xu X, Yang Y, Yi Q, Guo F, Li J, Zhou J and Kou Q: Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells. Oncol Rep 38: 3137-3143, 2017.
APA
Kou, B., Liu, W., Xu, X., Yang, Y., Yi, Q., Guo, F. ... Kou, Q. (2017). Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells. Oncology Reports, 38, 3137-3143. https://doi.org/10.3892/or.2017.5988
MLA
Kou, B., Liu, W., Xu, X., Yang, Y., Yi, Q., Guo, F., Li, J., Zhou, J., Kou, Q."Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells". Oncology Reports 38.5 (2017): 3137-3143.
Chicago
Kou, B., Liu, W., Xu, X., Yang, Y., Yi, Q., Guo, F., Li, J., Zhou, J., Kou, Q."Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells". Oncology Reports 38, no. 5 (2017): 3137-3143. https://doi.org/10.3892/or.2017.5988
Copy and paste a formatted citation
x
Spandidos Publications style
Kou B, Liu W, Xu X, Yang Y, Yi Q, Guo F, Li J, Zhou J and Kou Q: Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells. Oncol Rep 38: 3137-3143, 2017.
APA
Kou, B., Liu, W., Xu, X., Yang, Y., Yi, Q., Guo, F. ... Kou, Q. (2017). Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells. Oncology Reports, 38, 3137-3143. https://doi.org/10.3892/or.2017.5988
MLA
Kou, B., Liu, W., Xu, X., Yang, Y., Yi, Q., Guo, F., Li, J., Zhou, J., Kou, Q."Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells". Oncology Reports 38.5 (2017): 3137-3143.
Chicago
Kou, B., Liu, W., Xu, X., Yang, Y., Yi, Q., Guo, F., Li, J., Zhou, J., Kou, Q."Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells". Oncology Reports 38, no. 5 (2017): 3137-3143. https://doi.org/10.3892/or.2017.5988
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