Recent media interest in the PCa study that showed that aggressive cancer cells are fat factories, is a reminder that fatty acid synthase [FAS / FASN] upregulation is a feature of a number of cancers, & has been the subject of cancer research for over 20 years.
If we can reduce FAS levels in PCa cells, we can slow progression & metastasis.
[1] (2004) - Belgium.
{Note that epigallocatechin-3-gallate [EGCG] is the important polyphenol in green tea.}
"Based on our previous finding that the cytotoxic effect of the flavanol epigallocatechin-3-gallate on prostate cancer cells correlates with its ability to inhibit fatty acid synthase (FAS, a key lipogenic enzyme overexpressed in many human cancers), we examined the anti-lipogenic effects of a panel of 18 naturally occurring polyphenolic compounds. In addition to epigallocatechin-3-gallate, five other flavonoids, more particularly luteolin, quercetin, kaempferol, apigenin, and taxifolin, also markedly inhibited cancer cell lipogenesis. Interestingly, in both prostate and breast cancer cells, a remarkable dose-response parallelism was observed between flavonoid-induced inhibition of fatty acid synthesis, inhibition of cell growth, and induction of apoptosis. In support for a role of fatty acid synthesis in these effects, the addition of exogenous palmitate, the end product of FAS, markedly suppressed the cytotoxic effects of flavonoids. Taken together, these findings indicate that the potential of flavonoids to induce apoptosis in cancer cells is strongly associated with their FAS inhibitory properties, thereby providing a new mechanism by which polyphenolic compounds may exert their cancer-preventive and antineoplastic effects."
Note that palmitate is a form of palmitic acid, a saturated fat with a backbone of 16 carbons. Palmitic acid is the favored energy source of normal prostate cells, & this generally remains so in PCa - i.e. they do not switch to glucose.
Palmitic acid is found in many foods. It is the major fatty acid in palm oil. Can we avoid it via a low-fat diet? Alas, "Excess carbohydrates in the body are converted to palmitic acid." [2] It is the starting point for the synthesis of more complex longer chain fatty acids.
Discussion of diet in the context of FASN diverts us from the serious issue - that PCa cells can make almost any fatty acid that they need (excluding the "essential" omega-3 & omega-6 fatty acids), & their needs ultimately outstrip what they have access to from the circulation. FAS upregulation is essential to aggressive PCa, so any degree of inhibition is worthwhile.
"... assays showed that after 5 h of exposure of LNCaP cells to luteolin, quercetin, or kaempferol, a significant decrease in lipid synthesis was already evident at a concentration of 6 μM. Higher concentrations further reduced lipogenesis in a dose-dependent way. A further decline was observed after 24 h of exposure. At 12 μM, luteolin reduced lipogenesis to less than 10% of the control levels, thereby making luteolin the most efficient inhibitor of the studied flavonoids. EGCG was clearly less active ..."
Luteolin (not to be confused with the useful lutein) - possible source: [3].
Other studies of FAS inhibitors report that they do not all work the same way. There may be synergy in combining flavonoid polyphenols. FAS inhibition increases with dosage, & polyphenols are generally well-tolerated at higher doses. Green tea is an exception - it can elevate liver enzymes.
-Patrick
[1] jbc.org/content/280/7/5636....
Yes, dietary sugar can "feed" PC? (And heart disease!)
