題名:Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated human breast cancer cells via the regulation of EGFR/ErbB-2 signaling
作者:何元順
Meng-Shih Weng; Chi-Tang Ho; Yuan-Soon Ho; Jen-Kun Lin 貢獻者:醫學檢驗暨生物技術學系
上傳時間:2009-08-25T02:39:09Z
摘要:Fatty acid synthase (FAS) is a major lipogenic enzyme catalyzing the synthesis of long-chain saturated fatty acids. Most breast cancers require
lipogenesis for growth. Here, we demonstrated the effects of theanaphthoquinone (TNQ), a member of the thearubigins generated by the oxidation
of theaflavin (TF-1), on the expression of FAS in human breast cancer cells. TNQ was found to suppress the EGF-induced expression of FAS
mRNA and FAS protein in MDA-MB-231 cells. Expression of FAS has previously been shown to be regulated by the SREBP family of
transcription factors. In this study, we demonstrated that the EGF-induced nuclear translocation of SREBP-1 was blocked by TNQ. Moreover,
TNQ also modulated EGF-induced ERK1/2 and Akt
phosphorylation. Treatment of MDA-MB-231 cells with PI 3-kinase inhibitors, LY294002
and Wortmannin, inhibited the EGF-induced expression of FAS and nuclear translocation of SREBP-1. Treatment with TNQ inhibited EGFinduced
EGFR/ErbB-2 phosphorylation and dimerization.
Furthermore, treatment with kinase inhibitors of EGFR and ErbB-2 suggested that
EGFR/ErbB-2 activation was involved in EGF-induced FAS expression. In constitutive FAS expression, TNQ
inhibited FAS expression and Akt
autophosphorylation in BT-474 cells. The PI 3-kinase inhibitors and tyrosine kinase inhibitors of EGFR and
ErbB-2 also reduced constitutive FAS
expression. In addition, pharmacological blockade of FAS by TNQ decreased cell viability and induced cell death in BT-474 cells. In summary,
our findings suggest that TNQ modulates FAS expression by the regulation of EGFR/ErbB-2 pathways and induces cell death in breast cancer
