Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects.
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.
Yeh
C-W
CW
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
W-J
WJ
Chiang
C-T
CT
Lin-Shiau
S-Y
SY
Lin
J-K
JK
D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols; D013662:Tea
D004791:Enzyme Inhibitors; D005419:Flavonoids; D000960:Hypolipidemic Agents; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; D064429:Fatty Acid Synthases