Original Article
The Pharmacogenomics Journal (2003) 3, 267–276, doi:10.1038/sj.tpj.6500192 Published online 19 August 2003
Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects
C-W Yeh1, W-J Chen1, C-T Chiang1, S-Y Lin-Shiau2 and J-K Lin1
- 1Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan
- 2Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
Correspondence: J-K Lin, Institute of Biochemistry, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-ai Road, Taipei, Taiwan. Tel: +886 2 2356 2213; Fax: +886 2 2391 8944; E-mail: jklin@ha.mc.ntu.edu.tw
Received 31 January 2003; Revised 20 June 2003; Accepted 25 June 2003; Published online 19 August 2003.
Abstract
Tea is a heavily consumed beverage world wide because of its unique aroma, less cost and broad availability. Fatty acid synthase (FAS) is a key enzyme in lipogenesis. FAS is overexpressed in the malignant human breast carcinoma MCF-7 cells and its expression is further enhanced by the epidermal growth factor (EGF). The EGF-induced expression of FAS was inhibited by green and black tea extracts. The expression of FAS was also suppressed by the tea polyphenol (-)-epigallocatechin 3-gallate (EGCG), theaflavin (TF-1), TF-2 and theaflavin 3,3'-digallate(TF-3) at both protein and mRNA levels that may lead to the inhibition of cell lipogenesis and proliferation. Both EGCG and TF-3 inhibit the activation of Akt and block the binding of Sp-1 to its target site. Furthermore, the EGF-induced biosyntheses of lipids and cell proliferation were significantly suppressed by EGCG and TF-3. These findings suggest that tea polyphenols suppress FAS expression by downregulating EGF receptor/PI3K/Akt/Sp-1 signal transduction pathway, and tea and tea polyphenols might induce hypolipidemic and antiproliferative effects by suppressing FAS.
Keywords:
FAS, EGF, MCF-7 breast cancer cell, tea polyphenols, lipogenesis, proliferation, PI3K/Akt/Sp-1 signalling
