Einflüsse kurzkettiger und gesättigter langkettiger Fettsäuren auf das Tumorwachstum – In-vitro- und experimentelle In-vivo-Effekte

Zusammenfassung

Bei den derzeitigen Ernährungsempfehlungen für Patienten mit Malignomen wird zunehmend in Betracht gezogen, dass Tumorkrankheiten durch einen fettgestützten Stoffwechsel mit erheblich gestörter Glukoseverwertung gekennzeichnet sind. Fett sollte somit das bevorzugte energetische Substrat sein. Die Frage jedoch, welche einzelnen Fette sich besonders anbieten, und welche besser vermieden werden, lässt sich nur auf der Basis von Befunden der Nährstoffpharmakologie beantworten. Im vorliegenden Übersichtsartikel werden Einflüsse der kurzkettigen und der gesättigten langkettigen Fettsäuren auf das Tumorwachstum skizziert. Die kurzkettigen Fettsäuren, besonders Butyrat, interferieren mit dem Tumorwachstum, indem sie die Proliferation hemmen, die Zelldifferenzierung und die Apoptose aber begünstigen. Außerdem verringern sie die Angiogenese, die Invasivität und die Metastasierung. Diese Effekte wurden an Zelllinien vieler Neoplasien, aber auch in vivo regelmäßig beobachtet. Vermittelnd wirkt sich hier eine veränderte Expression regulatorischer Proteine und der Kaspasen aus, wobei die betreffenden Vorgänge wohl durch eine Hemmung der Histon-Deazetylierung bedingt sind. Da die Halbwertszeit des Butyrats nur ungefähr 6 Minuten beträgt, zieht man Tributyrin (Glyzerin-Tributyrat) dem Butyrat vor. Butyrat entsteht im Übrigen bei der intestinalen bakteriellen Fermentierung der Ballaststoffe, z. B. des Pektins. Durch die gesättigten langkettigen Fettsäuren, in erster Linie durch Palmitat und Stearat, wird ebenfalls die Proliferation maligner Zellen vermindert und die Apoptoserate gesteigert, sodass das Tumorwachstum abnimmt. Als Mechanismen dieser Wirkungen dürften eine Hemmung der Glykolyse und eine Beeinträchtigung der Fettsäurensynthese in den Malignomen im Vordergund stehen. Die gesättigten langkettigen Fettsäuren sind in Milch, Butter und mehreren anderen Nahrungsfetten in nennenswerten Mengen enthalten.

Abstract

Current nutritional recommendations for patients having a malignancy tend to take into account that the metabolism of energy-yielding substrates is lipid-based, and that glucose utilization is severely impaired. Fat should thus be the preferred energy substrate. However, in order to determine which types of fat are either advisable or should be avoided, it is necessary to consider data from nutrient pharmacology. In the present review article, the effects of short-chain as well as saturated long-chain fatty acids on tumor growth are outlined. Short-chain fatty acids, in particular butyrate, interfere with tumor growth by both inhibiting proliferation and promoting cell differentiation and also apoptosis. In addition, angiogenesis, invasion and metastasis are reduced. These effects were consistently observed not only in many tumor cell lines, but also in vivo. They are mediated by an altered expression of regulatory proteins and caspases and are probably due to an inhibition of histone deacetylation. Since the half-life of butyrate is only about 6 minutes, tributyrin (glycerol tributyrate) may be used instead. Furthermore, butyrate becomes available from the bacterial fermentation of dietary fiber, e. g. of pectin in the gut. Saturated long-chain fatty acids, especially palmitate and stearate also decrease the proliferation rate of malignant cells and induce apoptosis, thus retarding tumor growth. An inhibition of both glycolysis and fatty acid synthesis in malignancies may be the predominant mechanisms of these effects. Saturated long-chain fatty acids such as palmitate and stearate are found particularly in milk, butter and several other dietary fats.

Schlüsselwörter

kurzkettige Fettsäuren - Tributyrin - Palmitinsäure - Stearinsäure - Tumorwachstum - Nährstoffpharmakologie

Key words

short-chain fatty acids - tributyrin - palmitic acid - stearic acid - tumor growth - nutrient pharmacology

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