Resveratrol suppresses colon cancer growth by targeting the AKT/STAT3 signaling pathway

Dan Li, Gangcheng Wang, Guoguo Jin, Ke Yao, Zhenjiang Zhao, Liangyu Bie, Yongjun Guo, Ning Li, Wenying Deng, Xiaobin Chen, Beibei Chen, Yuanyuan Liu, Suxia Luo, Zhiping Guo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Colon cancer is a common type of cancer worldwide and accounts for a significant number of cancer‑related deaths. Although surgical techniques and treatment strategies for colon cancer have advanced over the past two decades, the prognosis has not improved considerably. Resveratrol, a natural stilbene compound, possesses antioxidant, cardioprotective and anticancer properties. However, the role of resveratrol in colon cancer has not been fully elucidated. The present study demonstrated that resveratrol inhibited cell proliferation and colony growth in DLD1 and HCT15 colon cancer cells, but did not affect normal colon epithelial cells. The resveratrol‑mediated inhibition of cell proliferation correlated with an induction of apoptosis and with G1 phase cell cycle arrest in colon cancer cells. Additionally, resveratrol treatment decreased the protein expression levels of cyclin D1, cyclin E2 and BCL2 apoptosis regulator, while it increased BCL2 associated X and tumor protein p53, all of which are involved in the regulation of cell cycle and apoptosis. Notably, the results obtained from in silico computational screening identified AKT serine/threonine kinase 1 (AKT1) and AKT2 as novel targets of resveratrol. Computational docking suggested that there are three or four possible hydrogen bonds in the active pocket of AKT1 and AKT2 that contribute to the mode of action of resveratrol. The present study confirmed that resveratrol bound to AKT1 and AKT2 with a pull‑down assay. Furthermore, knockdown of AKT1 and AKT2 inhibited cell proliferation and colony growth, by attenuating cell cycle progression and increasing apoptosis in colon cancer cells, effects that were similar to those caused by resveratrol treatment. Taken together, the present results suggest that the targeting effects of resveratrol to AKT1 and AKT2 may be a potent strategy for chemoprevention or therapy for colon cancer.

Original languageEnglish (US)
Pages (from-to)630-640
Number of pages11
JournalInternational journal of molecular medicine
Volume43
Issue number1
DOIs
StatePublished - Jan 2019
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Medical Science Research projects of Henan Province (grant no. 201702248), the Science and Technology Research Projects of Henan Province (grant no. 182102310376) and the Science and Technology Research Projects of Henan Province (grant no. 182102310125).

Publisher Copyright:
© 2019 Spandidos Publications. All rights reserved.

Keywords

  • AKT serine/threonine kinase
  • Colon cancer
  • Resveratrol
  • Signal transducer and activator of transcription 3
  • Signaling pathway

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