Limits...
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 inhibits AKT and mTOR, in addition to their downstream targets. EC-109 cells were treated with 25 µM VES for 12, 24 and 48 h. (A) Protein expression levels of p-AKT (Ser473 and Thr308), p-Bad (Ser136), p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were detected by western blotting. (B) Protein expression levels of p-mTOR (Ser2448), p-p70S6K (Thr389), and p-4E-BP1 (Thr37/46), and expression levels of total mTOR, p70S6 K and 4E-BP1 were determined by western blotting. (C) Protein expression levels were quantified and presented as the mean ± standard error of the mean. VES, vitmain E succinate; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; 4E-BP1, eIF4E-binding protein 1; Ctrl, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4940098&req=5

f3-mmr-14-02-1531: VES inhibits AKT and mTOR, in addition to their downstream targets. EC-109 cells were treated with 25 µM VES for 12, 24 and 48 h. (A) Protein expression levels of p-AKT (Ser473 and Thr308), p-Bad (Ser136), p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were detected by western blotting. (B) Protein expression levels of p-mTOR (Ser2448), p-p70S6K (Thr389), and p-4E-BP1 (Thr37/46), and expression levels of total mTOR, p70S6 K and 4E-BP1 were determined by western blotting. (C) Protein expression levels were quantified and presented as the mean ± standard error of the mean. VES, vitmain E succinate; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; 4E-BP1, eIF4E-binding protein 1; Ctrl, control.

Mentions: EC109 cells that are not treated with VES express high levels of p-AKT, and downstream substrates p-Bad and p-caspase-9 (Fig. 3). EC109 cells were treated with 25 µM VES for 12, 24 and 48 h, which reduced levels of p-AKT (Ser473/Thr308), p-Bad (Ser136), and p-caspase-9 (Ser196) in a time-dependent manner (Fig. 3A and C). It also downregulated p-mTOR (Ser2448) and its substrates p-p70S6K (Thr389) and p-4E-BP1 (Thr37/46; Fig. 3B and C). These data demonstrated that VES reduced the levels of active AKT, mTOR, and their downstream effectors, promoting the activation of Bad and caspase-9, which mediate cell apoptosis.


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 inhibits AKT and mTOR, in addition to their downstream targets. EC-109 cells were treated with 25 µM VES for 12, 24 and 48 h. (A) Protein expression levels of p-AKT (Ser473 and Thr308), p-Bad (Ser136), p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were detected by western blotting. (B) Protein expression levels of p-mTOR (Ser2448), p-p70S6K (Thr389), and p-4E-BP1 (Thr37/46), and expression levels of total mTOR, p70S6 K and 4E-BP1 were determined by western blotting. (C) Protein expression levels were quantified and presented as the mean ± standard error of the mean. VES, vitmain E succinate; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; 4E-BP1, eIF4E-binding protein 1; Ctrl, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-mmr-14-02-1531: VES inhibits AKT and mTOR, in addition to their downstream targets. EC-109 cells were treated with 25 µM VES for 12, 24 and 48 h. (A) Protein expression levels of p-AKT (Ser473 and Thr308), p-Bad (Ser136), p-caspase-9 (Ser196), and expression levels of total AKT, Bad and caspase-9 were detected by western blotting. (B) Protein expression levels of p-mTOR (Ser2448), p-p70S6K (Thr389), and p-4E-BP1 (Thr37/46), and expression levels of total mTOR, p70S6 K and 4E-BP1 were determined by western blotting. (C) Protein expression levels were quantified and presented as the mean ± standard error of the mean. VES, vitmain E succinate; AKT, serine-threonine kinase AKT; mTOR, mammalian target of rapamycin; p, phosphorylated; Bad, Bcl-2-associated death promoter; p70S6K, ribosomal protein S6 kinase β1; 4E-BP1, eIF4E-binding protein 1; Ctrl, control.
Mentions: EC109 cells that are not treated with VES express high levels of p-AKT, and downstream substrates p-Bad and p-caspase-9 (Fig. 3). EC109 cells were treated with 25 µM VES for 12, 24 and 48 h, which reduced levels of p-AKT (Ser473/Thr308), p-Bad (Ser136), and p-caspase-9 (Ser196) in a time-dependent manner (Fig. 3A and C). It also downregulated p-mTOR (Ser2448) and its substrates p-p70S6K (Thr389) and p-4E-BP1 (Thr37/46; Fig. 3B and C). These data demonstrated that VES reduced the levels of active AKT, mTOR, and their downstream effectors, promoting the activation of Bad and caspase-9, which mediate cell apoptosis.

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