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

Yang P, Zhao J, Hou L, Yang L, Wu K, Zhang L - Mol Med Rep (2016)

Bottom Line: 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.Furthermore, the current study suggests that VES may be useful in a combinational therapeutic strategy employing an mTOR inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus

VES induces apoptosis in human esophageal cancer cells in a dose- and time-dependent manner. (A) EC-109 cells were treated with different concentrations of VES for 24 h and the apoptosis induced by VES was determined by FACS assay. *P<0.05 vs. VES treatment group. (B) Cells were treated with 25 µM VES for different times, and untreated control cells were cultured for 48 h. The apoptosis induced by VES was assessed by FACS assay. Data are presented as the mean ±standard error of the mean *P<0.05 vs. ctrl group. VES, vitamin E succinate; FACS, fluorescence-activated cell sorting; Ctrl, control.
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f2-mmr-14-02-1531: VES induces apoptosis in human esophageal cancer cells in a dose- and time-dependent manner. (A) EC-109 cells were treated with different concentrations of VES for 24 h and the apoptosis induced by VES was determined by FACS assay. *P<0.05 vs. VES treatment group. (B) Cells were treated with 25 µM VES for different times, and untreated control cells were cultured for 48 h. The apoptosis induced by VES was assessed by FACS assay. Data are presented as the mean ±standard error of the mean *P<0.05 vs. ctrl group. VES, vitamin E succinate; FACS, fluorescence-activated cell sorting; Ctrl, control.

Mentions: To investigate whether VES promotes apoptosis in esophageal cancer cells, EC109 cells were treated with VES at various concentrations (0, 10 or 100 µM; Fig. 2A) or for different periods of time (12, 24 or 48 h; Fig. 2B). Apoptosis was quantified by FACS analyses. Apoptosis in the EC109 cells was induced by 10 or 100 µM VES treatment for 24 h in a dose-dependent manner (Fig. 2A). Apoptosis of EC109 cells was induced by 25 µM VES for 12, 24 and 48 h in a time-dependent manner (Fig. 2B). These results suggest that VES is a potent inducer of apoptosis in EC109 esophageal cancer cells.


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

Yang P, Zhao J, Hou L, Yang L, Wu K, Zhang L - Mol Med Rep (2016)

VES induces apoptosis in human esophageal cancer cells in a dose- and time-dependent manner. (A) EC-109 cells were treated with different concentrations of VES for 24 h and the apoptosis induced by VES was determined by FACS assay. *P<0.05 vs. VES treatment group. (B) Cells were treated with 25 µM VES for different times, and untreated control cells were cultured for 48 h. The apoptosis induced by VES was assessed by FACS assay. Data are presented as the mean ±standard error of the mean *P<0.05 vs. ctrl group. VES, vitamin E succinate; FACS, fluorescence-activated cell sorting; Ctrl, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940098&req=5

f2-mmr-14-02-1531: VES induces apoptosis in human esophageal cancer cells in a dose- and time-dependent manner. (A) EC-109 cells were treated with different concentrations of VES for 24 h and the apoptosis induced by VES was determined by FACS assay. *P<0.05 vs. VES treatment group. (B) Cells were treated with 25 µM VES for different times, and untreated control cells were cultured for 48 h. The apoptosis induced by VES was assessed by FACS assay. Data are presented as the mean ±standard error of the mean *P<0.05 vs. ctrl group. VES, vitamin E succinate; FACS, fluorescence-activated cell sorting; Ctrl, control.
Mentions: To investigate whether VES promotes apoptosis in esophageal cancer cells, EC109 cells were treated with VES at various concentrations (0, 10 or 100 µM; Fig. 2A) or for different periods of time (12, 24 or 48 h; Fig. 2B). Apoptosis was quantified by FACS analyses. Apoptosis in the EC109 cells was induced by 10 or 100 µM VES treatment for 24 h in a dose-dependent manner (Fig. 2A). Apoptosis of EC109 cells was induced by 25 µM VES for 12, 24 and 48 h in a time-dependent manner (Fig. 2B). These results suggest that VES is a potent inducer of apoptosis in EC109 esophageal cancer cells.

Bottom Line: 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.Furthermore, the current study suggests that VES may be useful in a combinational therapeutic strategy employing an mTOR inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus