Open Access

Diosmetin inhibits cell proliferation and induces apoptosis by regulating autophagy via the mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells

  • Authors:
    • Jie Liu
    • Hao Ren
    • Bin Liu
    • Qingyu Zhang
    • Mingyi Li
    • Runzhi Zhu
  • View Affiliations

  • Published online on: October 19, 2016     https://doi.org/10.3892/ol.2016.5301
  • Pages: 4385-4392
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC), which is a type of malignant tumor, is the fifth most common cancer in men and ninth in women worldwide. The aim of the present study was to investigate the antitumor effect of diosmetin (DIOS) in hepatocellular carcinoma HepG2 cells. The proliferation, apoptosis and autophagy rates of HepG2 cells were measured following treatment with DIOS. The effects of DIOS treatment on HepG2 cell proliferation and apoptosis rates were analyzed using MTT assays and Annexin V staining, respectively. The effect of DIOS treatment on autophagy levels was assessed using transmission electron microscopy, green fluorescent protein (GFP)‑microtubule‑associated protein 1 light chain (LC3) transfection and LysoTracker Red staining. Furthermore, bafilomycin A1 (BA1), an autophagy inhibitor, was used to assess the association between DIOS and cell autophagy, proliferation and apoptosis. In addition, the expression of autophagy‑related proteins [mammalian target of rapamycin (mTOR), phosphatidylinositol 3‑kinase, P70S6K, phosphoinositide‑dependent kinase‑1, extracellular signal‑regulated kinase, 5'‑AMP‑activated protein kinase and Akt] and apoptosis‑related proteins [B‑cell lymphoma (Bcl)‑2‑associated X protein, Bak, p53, Bcl‑2 and caspase‑3] were analyzed by western blotting. The results revealed that DIOS significantly inhibited proliferation (P<0.01) and induced apoptosis (P<0.001) in HepG2 cells. It was also demonstrated that DIOS triggered autophagy by regulating the mTOR pathway in HepG2 cells. Notably, following treatment of HepG2 cells with the autophagy inhibitor, BA1, the expression of apoptosis‑related proteins, including Bax, Bak and p53, were significantly decreased (P<0.05), and cell viability was recovered to a certain extent. In conclusion, DIOS inhibits cell proliferation and induces apoptosis in HepG2 cells via regulation of the mTOR pathway. Thus, the results of the current study indicate that DIOS may present a potential therapeutic agent for HCC treatment.
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December-2016
Volume 12 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Liu J, Ren H, Liu B, Zhang Q, Li M and Zhu R: Diosmetin inhibits cell proliferation and induces apoptosis by regulating autophagy via the mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells. Oncol Lett 12: 4385-4392, 2016
APA
Liu, J., Ren, H., Liu, B., Zhang, Q., Li, M., & Zhu, R. (2016). Diosmetin inhibits cell proliferation and induces apoptosis by regulating autophagy via the mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells. Oncology Letters, 12, 4385-4392. https://doi.org/10.3892/ol.2016.5301
MLA
Liu, J., Ren, H., Liu, B., Zhang, Q., Li, M., Zhu, R."Diosmetin inhibits cell proliferation and induces apoptosis by regulating autophagy via the mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells". Oncology Letters 12.6 (2016): 4385-4392.
Chicago
Liu, J., Ren, H., Liu, B., Zhang, Q., Li, M., Zhu, R."Diosmetin inhibits cell proliferation and induces apoptosis by regulating autophagy via the mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells". Oncology Letters 12, no. 6 (2016): 4385-4392. https://doi.org/10.3892/ol.2016.5301