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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

AKT and mTOR are downstream targets of PI3K. EC109 cells were treated with 2 µM PI3K inhibitor (PI3KI) LY294002 for 12 h. (A) Protein expression levels of p-AKT (Ser473), p-Bad (Ser136) and p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were determined by western blotting. (B) Protein expression levels of p-mTOR (Ser2448) and p-p70S6K (Thr389), and total levels of mTOR and p70S6K were also determined by western blotting. PI3K, phosphoinositide-3-kinase; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; Ctrl, control.
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f4-mmr-14-02-1531: AKT and mTOR are downstream targets of PI3K. EC109 cells were treated with 2 µM PI3K inhibitor (PI3KI) LY294002 for 12 h. (A) Protein expression levels of p-AKT (Ser473), p-Bad (Ser136) and p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were determined by western blotting. (B) Protein expression levels of p-mTOR (Ser2448) and p-p70S6K (Thr389), and total levels of mTOR and p70S6K were also determined by western blotting. PI3K, phosphoinositide-3-kinase; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; Ctrl, control.

Mentions: To investigate the underlying mechanisms of regulation of the levels of p-AKT and p-mTOR, EC109 cells were treated with 2 µM PI3K inhibitor LY294002 for 12 h. LY294002 decreased the p-AKT and its substrates p-Bad (Ser136) and p-caspase-9 (Ser196; Fig. 4A), in addition to p-mTOR (Ser2448) and its substrate p-p70S6 K (Thr389) (Fig. 4B). This indicates that PI3K is a key contributor to regulations of p-AKT and p-mTOR.


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)

AKT and mTOR are downstream targets of PI3K. EC109 cells were treated with 2 µM PI3K inhibitor (PI3KI) LY294002 for 12 h. (A) Protein expression levels of p-AKT (Ser473), p-Bad (Ser136) and p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were determined by western blotting. (B) Protein expression levels of p-mTOR (Ser2448) and p-p70S6K (Thr389), and total levels of mTOR and p70S6K were also determined by western blotting. PI3K, phosphoinositide-3-kinase; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; Ctrl, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-mmr-14-02-1531: AKT and mTOR are downstream targets of PI3K. EC109 cells were treated with 2 µM PI3K inhibitor (PI3KI) LY294002 for 12 h. (A) Protein expression levels of p-AKT (Ser473), p-Bad (Ser136) and p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were determined by western blotting. (B) Protein expression levels of p-mTOR (Ser2448) and p-p70S6K (Thr389), and total levels of mTOR and p70S6K were also determined by western blotting. PI3K, phosphoinositide-3-kinase; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; Ctrl, control.
Mentions: To investigate the underlying mechanisms of regulation of the levels of p-AKT and p-mTOR, EC109 cells were treated with 2 µM PI3K inhibitor LY294002 for 12 h. LY294002 decreased the p-AKT and its substrates p-Bad (Ser136) and p-caspase-9 (Ser196; Fig. 4A), in addition to p-mTOR (Ser2448) and its substrate p-p70S6 K (Thr389) (Fig. 4B). This indicates that PI3K is a key contributor to regulations of p-AKT and p-mTOR.

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