alpha-Tocopheryl succinate induces apoptosis in erbB2-expressing breast cancer cell via NF-kappa B pathway

作者：Wang, Xiu-fang^*; Xie, Ying; Wang, Hong-gang; Zhang, Yuan; Duan, Xiao-cui; Lu, Zhan-jun

来源：Acta Pharmacologica Sinica, 2010, 31(12): 1604-1610.

DOI：10.1038/aps.2010.171

• erbB2
• alpha-TOS
• breast cancer
• NF-kappa B
• apoptosis
• hrTRAIL

Aim: To study the molecular mechanisms underlying alpha-tocopheryl succinate (alpha-TOS)-induced apoptosis in erbB2-positive breast cancer cells and to determine whether alpha-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 alpha-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-kappa B p65 kit was used to assess NF-kappa B activation.
Results: alpha-TOS (100 mu mol/L) significantly inhibited NF-kappa B nuclear translocation in erbB2-expressing breast cancer cells; this inhibition is expected to result in the inactivation of NF-kappa B. alpha-TOS (50 and 100 mu mol/L) inhibited the expression of Flice-like inhibitory protein (FLIP) and cellular inhibitor of apoptosis protein 1 (c-IAP1) in erbB2-positive cells. alpha-TOS (100 mu mol/L) inhibited Akt activation and augmented the activity of caspase 3 and caspase 8 in breast cancer cells expressing erbB2. alpha-TOS (50 mu mol/L) and hrTRAIL (30 mg/mL) acted synergically to induce apoptosis in breast cancer cells. alpha-TOS also decreased the hrTRAIL-induced transient activation of NF-kappa B.
Conclusion: Our results suggest that alpha-TOS mediates the apoptosis of erbB2-positive breast cancer cells and acts synergically with hrTRAIL via the NF-kappa B pathway.

• 出版日期2010-12
• 单位河南大学; 河北医科大学