Vitamin E succinate induces apoptosis via the PI3K/AKT signaling pathways in EC109 esophageal cancer cells

Yang,Peng; Zhao,Jiaying; Hou,Liying; Yang,Lei; Wu,Kun; Zhang,Linyou

doi:10.3892/mmr.2016.5445

Vitamin E succinate induces apoptosis via the PI3K/AKT signaling pathways in EC109 esophageal cancer cells

Authors:
- Peng Yang
- Jiaying Zhao
- Liying Hou
- Lei Yang
- Kun Wu
- Linyou Zhang
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Affiliations: Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Nutrition and Food Hygiene, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
Published online on: June 27, 2016 https://doi.org/10.3892/mmr.2016.5445
Pages: 1531-1537
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Esophageal cancer is the fourth most common gastrointestinal cancer, it generally has a poor prognosis and novel strategies are required for prevention and treatment. Vitamin E succinate (VES) is a potential chemical agent for cancer prevention and therapy as it exerts anti‑tumor effects in a variety of cancers. However, the role of VES in tumorigenesis and progression of cancer remains to be elucidated. The present study aimed to determine the effects of VES in regulating the survival and apoptosis of human esophageal cancer cells. EC109 human esophageal cancer cells were used to investigate the anti‑proliferative effects of VES. The MTT and Annexin V‑fluorescein isothiocyanate/propidium iodide assays demonstrated that VES inhibited cell proliferation and induced apoptosis in esophageal cancer cells. Furthermore, VES downregulated constitutively active basal levels of phosphorylated (p)‑serine‑threonine kinase AKT (AKT) and p‑mammalian target of rapamycin (mTOR), and decreased the phosphorylation of AKT substrates Bcl‑2‑associated death receptor and caspase‑9, in addition to mTOR effectors, ribosomal protein S6 kinase β1 and eIF4E‑binding protein 1. Phosphoinositide‑3‑kinase (PI3K) inhibitor, LY294002 suppressed p‑AKT and p‑mTOR, indicating PI3K is a common upstream mediator. The apoptosis induced by VES was increased by inhibition of AKT or mTOR with their respective inhibitor in esophageal cancer cells. The results of the present study suggested that VES targeted the PI3K/AKT signaling pathways and induced apoptosis in esophageal cancer cells. Furthermore, the current study suggests that VES may be useful in a combinational therapeutic strategy employing an mTOR inhibitor.

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