The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 10 No.
1 • March 2007
Suppression of Fatty Acid Synthase in Breast Cancer Cells by Tea and Tea Polyphenols
Fatty acid synthase (FAS) is the final enzyme in the biochemical pathway for lipogenesis, synthesizing fats from glucose. It is highly conserved, as bacteria contain a version (FASII) of the same enzyme as is found in mammals. Importantly, FAS is overexpressed by many human cancers (such as breast, colon, ovary, lung, and prostate), and inhibition of FAS induces apoptosis (programmed cell death) in human cancer cells.
FAS inhibitors result in increased levels of malonyl-CoA, the substrate for FAS, because of reduced conversion of malonyl-CoA to fat. As we have discussed earlier, malonyl-CoA is an important signaling molecule that provides the brain with information concerning the availability of caloric fuel and thereby affects regulatory pathways for feeding and energy expenditure. When malonyl-CoA levels are high, feeding is suppressed and energy expenditure increased. In cancer cells, fatty acid synthesis is associated with markers of proliferation.
A recent paper reports that FAS is overexpressed in the malignant human breast carcinoma MCF-7 cells, and this expression is increased by concomitant expression of epidermal growth factor. In this study, the researchers found that, in cultures of MCF-7 cells, tea extracts from oolong, black, and green tea “seemed to stimulate the expression of FAS at a lower concentration (30 μg/ml). However, when the cells were exposed to a higher concentration of tea extracts (120 μg/ml), the expression of FAS was inhibited by green and black tea extracts, but not by the oolong tea extract.” Moreover, “In green tea catechins, only EGCG was found to reduce the amount of FAS protein significantly, by 76% at a dose of 30 μM … To our surprise, the black tea polyphenols TF-1, TF-2, and TF-3 [these are all theaflavins] actively downregulated FAS by 52, 69, and 87% at 30 μM, respectively. TF-3 was the most active in reducing the FAS protein.”
The authors also report that the suppression of epidermal growth factor-induced FAS protein by EGCG and TF-3 was also demonstrated in human hepatoblastoma HepG2 (a liver cancer line). Interestingly, they report that “It appeared that the expression of FAS in the HepG2 cells was more tightly regulated by insulin than by EGF [epidermal growth factor].” The insulin-enhanced FAS expression was significantly suppressed by EGCG and TF-3. The stimulation of FAS expression by insulin (at least in this human liver cancer line) may be one reason to suggest (as we have) that FAS inhibitors will work best with a low-glycemic-index diet.
It would also appear that the use of both green tea and black (fermented) tea would be most beneficial, as each type of tea contains its own (different) FAS inhibitors. It is not clear why oolong tea did not suppress FAS in this study; perhaps the particular type of oolong tea they used didn’t include the theaflavins as found in the black tea.
- Yeh et al. Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects. Pharmacogenom J 3:267-76 (2003).
- Thupari et al. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity. Biochem Biophys Res Commun 285:217-23 (2001).