Meng-Shih Weng |
------>authors3_c=??? ------>paper_class1=1 ------>Impact_Factor=4.722 ------>paper_class3=2 ------>paper_class2=1 ------>vol=218 ------>confirm_bywho=leehorng ------>insert_bywho=hoyuansn ------>Jurnal_Rank=5.3 ------>authors4_c=??? ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=118 ------>medlineContent= ------>unit=E0310 ------>insert_date=20071127 ------>iam=3 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c=??? ------>score=500 ------>journal_name=Toxicology and Applied Pharmacology ------>paper_name=Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated human breast cancer cells via the regulation of EGFR/ErbB-2 signaling ------>confirm_date=20071127 ------>tch_id=084007 ------>pmid=17182072 ------>page1=107 ------>fullAbstract=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 EGF-induced 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 cells. ------>tmu_sno=None ------>sno=16272 ------>authors2=Chi-Tang Ho ------>authors3=Yuan-Soon Ho ------>authors4=Jen-Kun Lin ------>authors5= ------>authors6= ------>authors6_c= ------>authors=Meng-Shih Weng ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=??? ------>publish_area=0 ------>updateTitle=Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated human breast cancer cells via the regulation of EGFR/ErbB-2 signaling. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2007 ------>submit_flag=None ------>publish_month=1 |