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25 november 2017: Bron: Nat Commun. 2017; 8: 922. Published online 2017 Oct 13.

Er wordt vaak gezegd dat suiker kanker veroorzaakt of erger maakt en de tumor laat groeien. Hiervoor was tot nu toe echter geen wetenschappelijk bewijs. Maar nu lijken Belgische onderzoekers ontrafelt te hebben dat suiker de groei van de tumor stimuleert en wel degelijk kanker agressiever maakt. Zelfs tijdens een chemokuur voedt suiker de tumorcellen extra waardoor de effectiviteit van chemo gedeeltelijk teniet wordt gedaan door de suiker. Of suiker ook kanker veroorzaakt zijn ze minder stellig want een gezond lichaam kan een heleboel repareren. Dit blijkt uit een 9 jaar lang onderzoek naar het Warburg effect van onderzoekers aan het Vlaams Instituut voor Biotechnologie (VIB), KULeuven en VUB. Zij legden bloot hoe kankercellen suiker versneld afbreken en hoe dat ­mechanisme er dan weer voor zorgt dat de kanker in stand wordt gehouden en er weer recidieven ontstaan en uitzaaiingen, vaak elders in het lichaam, opduiken.

“Het is een belangrijke doorbraak in het kankeronderzoek en een suikervrij of suikerarm dieet is voor een kanker­­pa­tiënt dus geen overbodige luxe”, zegt professor Johan Thevelein, mede onderderzoeker van deze studie: Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras.

In 2008 besloten prof. Thevelein en collega's om onderzoek te doen naar het zogeheten Warburg-effect. “Dr. Otto Warburg, een Duitse biochemicus, (het Houtsmullerdieet is mede gebaseerd op het Warburg effect), ontdekte al eindjaren dertig vorige eeuw dat kankercellen versneld suiker omzetten in melkzuur.

Prof. Thevelein: “Ze verkiezen eigenlijk suiker te vergisten naar melkzuur bóven te verademen naar koolstofdioxide.” Compleet het tegenovergestelde van gezonde cellen. “Hoe agressiever de kanker, hoe sneller die cellen dat doen. Maar waarom ze dat deden en of dat Warburg-effect louter een symptoom is van de kanker of er ook een invloed op uitoefent, dat wisten we niet. Wij wilden dat achterhalen.”

In het onderzoek werd eerst gekeken naar gistcellen. Een eenvoudige celvorm, die ook het Warburg-effect vertoont zegt prof. Thevelein, maar dan zonder de invloed van hormonen en andere regulatiesystemen die in kankercellen bij mensen de resultaten zouden kunnen vertroebelen.

"Nu wordt het even heel technisch", aldus prof. Thevelein: “In de gistcellen ontdekten we hoe bij die omzetting van suiker de molecule fructose 1,6-biofosfaat sterker in de cellen aangemaakt wordt. Die activeert dan weer een proteïne (eiweit) dat de cellen op hun beurt doet vermenigvuldigen. Dat mechanisme is daarna op de faculteit geneeskunde in menselijke kankercellen bevestigd”, zegt professor Thevelein.

"Ook voor kankercellen betekent het dus dat suiker kankercellen nog sneller doet vermenigvuldigen. De tumor groeit; de kanker wordt agressiever en deelt sneller. Met als effect dat er nog meer kankercellen suiker gaan omzetten. “Het is dus een vicieuze cirkel, die maakt dat de kanker moeilijker met geneesmiddelen te bestrijden is.”

Prof. Johan Thevelein is heel stellig over een suikerarm dieet voor kankerpatiënten: “Een suikervrij of suikerarm dieet blijkt niet zomaar een hype maar écht iets om op in te zetten bij kankerpatiënten. Het kan helpen de kanker te overwinnen en chemotherapie veel effectiever maken. Vooral ook omdat patiënten naast chemokuren soms extra voeding krijgen toegediend om aan te sterken. En die bevatten meestal veel glucosesuiker.”

Of suiker ook kanker kan veroorzaken en preventief kanker kan voorkomen is hij minder stellig: “Daarvoor is nog meer onderzoek nodig. Normale cellen hebben goede controlesystemen die ervoor zorgen dat de suikerafbraak in de cel binnen de perken blijft. Ze kunnen er doorgaans mee overweg. Of dat ook bij langdurige excessieve suikerinname zo is, blijft onduidelijk.”

Het studierapport is gepublicered in Nature: Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras.  en gratis in te zien.

CNN had een mooie reportage over de studie van prof Thevelein en collega's: Does sugar, which makes all things delicious, lead to cancer?

Hier het abstract van de studie met referentieliijst:

Sugar stimulates the aggressiveness of cancer

Nat Commun. 2017; 8: 922.
Published online 2017 Oct 13. doi:  10.1038/s41467-017-01019-z
PMCID: PMC5640605

Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras

Abstract

Yeast and cancer cells share the unusual characteristic of favoring fermentation of sugar over respiration. We now reveal an evolutionary conserved mechanism linking fermentation to activation of Ras, a major regulator of cell proliferation in yeast and mammalian cells, and prime proto-oncogene product. A yeast mutant (tps1∆) with overactive influx of glucose into glycolysis and hyperaccumulation of Fru1,6bisP, shows hyperactivation of Ras, which causes its glucose growth defect by triggering apoptosis. Fru1,6bisP is a potent activator of Ras in permeabilized yeast cells, likely acting through Cdc25. As in yeast, glucose triggers activation of Ras and its downstream targets MEK and ERK in mammalian cells. Biolayer interferometry measurements show that physiological concentrations of Fru1,6bisP stimulate dissociation of the pure Sos1/H-Ras complex. Thermal shift assay confirms direct binding to Sos1, the mammalian ortholog of Cdc25. Our results suggest that the Warburg effect creates a vicious cycle through Fru1,6bisP activation of Ras, by which enhanced fermentation stimulates oncogenic potency.

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