Source: Current Pharmaceutical Biotechnology (2006), 7: 483-494
Article Type: Review
Authors: R. Lupu, J.A. Menendez


Image taken from: http://herbal-nutrition.net/images/vegetables.jpg

Food plant-derived inhibitors of fatty acid synthase (FAS), such as EGCG (a polyphenol) from green tea, have been suggested as a new family of anti-cancer agents. In contrast to normal cells, tumor cells (especially those forming epithelial cancers) exhibit FAS hyperactivity to meet their increased demand of energy and membrane building blocks. Inhibition of FAS leads to tumor cell growth arrest and ultimately cell death (partly via apoptosis).
When talking about the inhibition of tumor cell growth and proliferation due to incubation with polyphenols (and related substances) one, however, has to keep in mind two potential pitfalls:
a) Polyphenols at medium to high concentration have been shown to cause artificially augmented release of cytotoxic reactive oxygen species (ROS) by reacting with various constituents of routinely used serum-supplemented culture media (Chai et al.).
b) The bioavailability of polyphenols is limited so that oral polyphenol intake gives plasma concentrations of approx. 0.5-5 µM. Many (actually too many) in vitro studies test polyphenol working solutions with concentrations far beyond the aforementioned physiological levels (Kroon et al.).
This are just two reasons for the failure of polyphenols to show their potentially health-beneficial effects in most intervention studies.
Now, Lupu & Menendez summarize recent data on the in vitro anti-tumor efficiency of polyphenols, i.e. quercetin, luteolin, kaempferol and EGCG, linked to the inhibition of FAS. At a concentration of 5 µM, these polpyhenols block FAS activity by >60% (Brusselmans et al.). Lupu & Menendez also provide an interesting overview on both molecular mechanisms (i.e. end-product starvation, accumulation of a toxic FAS substrate, altered membrane synthesis) as well as on molecular markers (i.e. p53, erbB-2 oncogene expression, PI-3′K/AKT pathway regulation) of FAS inhibition.
Thus, the pharmaconutritional regulation of FAS activity might represent a new alley for the diagnosis, prevention and possibly therapy of certain cancers.