α-Tocopheryl succinate induces apoptosis in erbB2-expressing breast cancer cell via NF-κB pathway.
Acta Pharmacol Sin
; 31(12): 1604-10, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-21127496
ABSTRACT
AIM:
to study the molecular mechanisms underlying α-tocopheryl succinate (α-TOS)-induced apoptosis in erbB2-positive breast cancer cells and to determine whether α-TOS and the human recombinant TNF-related apoptosis-inducing ligand (hrTRAIL) act synergically to induce cell death of erbB2-expressing breast cancer cells.METHODS:
the annexin V binding method was used to measure apoptosis induced by α-TOS and/or hrTRAIL. RT-PCR and Western blotting were performed to detect gene and protein expression. A colorimetric assay was performed to detect caspase activity. The TransAM(TM) NF-κB p65 kit was used to assess NF-κB activation.RESULTS:
α-TOS (100 µmol/L) significantly inhibited NF-κB nuclear translocation in erbB2-expressing breast cancer cells; this inhibition is expected to result in the inactivation of NF-κB. α-TOS (50 and 100 µmol/L) inhibited the expression of Flice-like inhibitory protein (FLIP) and cellular inhibitor of apoptosis protein 1 (c-IAP1) in erbB2-positive cells. α-TOS (100 µmol/L) inhibited Akt activation and augmented the activity of caspase 3 and caspase 8 in breast cancer cells expressing erbB2. α-TOS (50 µmol/L) and hrTRAIL (30 mg/mL) acted synergically to induce apoptosis in breast cancer cells. α-TOS also decreased the hrTRAIL-induced transient activation of NF-κB .CONCLUSION:
our results suggest that α-TOS mediates the apoptosis of erbB2-positive breast cancer cells and acts synergically with hrTRAIL via the NF-κB pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
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Apoptose
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Receptor ErbB-2
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Alfa-Tocoferol
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Antioxidantes
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article