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

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

doi:10.3892/ijmm.2018.3969

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

Authors:
- 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
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Affiliations: Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China, Laboratory of Bone Tumor, Henan Luoyang Orthopedic Hospital, Zhengzhou, Henan 450000, P.R. China, China‑US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450003, P.R. China, Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China, Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, P.R. China , Fu Wai Hua Zhong Vascular Disease Hospital, Zhengzhou, Henan 450018, P.R. China
Published online on: November 1, 2018 https://doi.org/10.3892/ijmm.2018.3969
Pages: 630-640

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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.

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