Open Access

Resveratrol inhibits proliferation and migration through SIRT1 mediated post‑translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells

  • Authors:
    • Rongfei Chai
    • Huiling Fu
    • Zhaodi Zheng
    • Tingting Liu
    • Shuhua Ji
    • Guorong Li
  • View Affiliations

  • Published online on: September 26, 2017     https://doi.org/10.3892/mmr.2017.7612
  • Pages:8037-8044
  • Copyright: © Chai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Resveratrol (RES), a polyphenolic compound present in grapes and red wine, has potential anticancer properties. The present study aimed to examine the effects of resveratrol and its underlying mechanism on hepatocellular carcinoma (HCC) cell lines HepG2, Bel‑7402 and SMMC‑7721. It was demonstrated that resveratrol inhibited the viability and proliferation of HCC cells assessed by MTT and EdU assays. TUNEL assay revealed that resveratrol induced cell apoptosis by increasing HCC apoptosis rate from 3±0.78% to 16±1.12% with upregulation of B‑cell lymphoma (Bcl)‑2 associated X, apoptosis regulator and cleaved‑poly (ADP‑Ribose) polymerase 1 (PARP), and downregulation of Bcl‑2, caspase‑3, caspase‑7 and PARP. As a sirtuin (SIRT) 1 activator, resveratrol elevated SIRT1 protein expression and its enzyme activity and decreased expression levels of phosphorylated (p)‑phosphoinositide‑3‑kinase (PI3K), p‑AKT Serine/Threonine Kinase 1 (AKT), and its downstream target p‑Forkhead Box O3a in HepG2 cells. Furthermore, inhibition of SIRT1 enzymatic activity by EX527 resulted in increased phosphorylation levels of PI3K and AKT. This demonstrated that resveratrol inhibited the PI3K/AKT pathway by SIRT1 activation. In addition to inhibition of cancer cell migration, tumor suppressor gene DLC1 Rho GTPase activating protein level was upregulated and its phosphorylation was enhanced by AKT with resveratrol treatment. These findings suggested that resveratrol inhibits proliferation and migration through SIRT1 mediated post‑translational modification of PI3K/AKT pathway in HCC cells.

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December 2017
Volume 16 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Chai, R., Fu, H., Zheng, Z., Liu, T., Ji, S., & Li, G. (2017). Resveratrol inhibits proliferation and migration through SIRT1 mediated post‑translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells. Molecular Medicine Reports, 16, 8037-8044. https://doi.org/10.3892/mmr.2017.7612
MLA
Chai, R., Fu, H., Zheng, Z., Liu, T., Ji, S., Li, G."Resveratrol inhibits proliferation and migration through SIRT1 mediated post‑translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells". Molecular Medicine Reports 16.6 (2017): 8037-8044.
Chicago
Chai, R., Fu, H., Zheng, Z., Liu, T., Ji, S., Li, G."Resveratrol inhibits proliferation and migration through SIRT1 mediated post‑translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells". Molecular Medicine Reports 16, no. 6 (2017): 8037-8044. https://doi.org/10.3892/mmr.2017.7612