Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects

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 (À)-epigallocatechin 3-gallate (EGCG), theaflavin (TF-1), TF-2 and theaflavin 3,3 0 -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.

Hypotriglyceridemic effect of Morus alba L., Moraceae, leaves in hyperlipidemic rats

“…Such effect has been demonstrated in experiments using M. alba root bark or fruit (Chen et al, 2005;El-Bebshbishy et al, 2006) and in other plants (Chan et al, 1999;Wang et al, 2000;Yeh et al, 2003).…”

Tea and Mint Extracts Modulate the HSP70 Expression in Preeclamptic Placental Explant

“…This beverage is consumed worldwide because of its unique aroma, low cost and wide availability (Yeh et al 2003). Tea contains high level of polyphenols and flavonoids which acts as an antioxidant and protects the cell from the oxidative damage by scavenging free radicals (Dufresne & Farnworth, 2001).…”

Pharmacogenomics: The Significance of Genetics in the Metabolism of Natural Medicines

“…It can lead to the overactivation of fatty enzymes in the body leading to slow metabolism and blood clot formation in cardiovascular health, or enzyme activation in cancer [5]. Fatty acid synthase (FAS) is an important enzyme in human metabolism, and studies have shown that the expression of FAS is highly increased in human cancer cells, including breast, colon, ovary, lung and prostate cancer.…”

“…Fatty acid synthase (FAS) is an important enzyme in human metabolism, and studies have shown that the expression of FAS is highly increased in human cancer cells, including breast, colon, ovary, lung and prostate cancer. The protein hormone, leptin, plays a major role in regulating FAS by inhibiting its function in the human body; however, in some patients, FAS has evolved showing resistant strains to leptin [5]. It has led to the research and development of leptin-like compounds, known as FASinhibitors, which produce cytotoxic effects similar to leptin by increasing malonyl-CoA levels in the hypothalamic neuron [5].…”

“…According to C.-W. Yeh et al, green tea contains six catechins, (+) catechin (C), (−)-epicatechin (EC), (−)-epicatechin 3-gallate (ECG), (−)-epigallocatechin (EGC), (−)-epigallocatechin 3-gallate (EGCG) and (−)-gallocatechin 3-gallate (GCG). While, the black tea polyphenols contained theaflavins such as theaflavin (TF-1), theaflavin 3-gallate (TF-2a), theaflavin 3'-gallate (TF-2b) and theaflavin 3,3'-digallate(TF-3) [5].…”