Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

Abstract

Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP). We provide evidence that acetate enters CRC cells by the secondary active transporters MCT1 and/or MCT2 and SMCT1 as well as by facilitated diffusion via aquaporins. CRC cell exposure to acetate upregulates the expression of MCT1, MCT4 and CD147, while promoting MCT1 plasma membrane localization. We also observed that acetate increases CRC cell glycolytic phenotype and that acetate-induced apoptosis and anti-proliferative effect was potentiated by 3BP. Our data suggest that acetate selectivity towards CRC cells might be explained by the fact that aquaporins and MCTs are found overexpressed in CRC clinical cases. Our work highlights the importance that acetate transport regulation has in the use of drugs such as 3BP as a new therapeutic strategy for CRC.

In vitro assessment of prebiotic properties of xylooligosaccharides produced by Bacillus subtilis 3610

“…The same evidence was found for lactulose (Ito et al, 1997;Fernandes et al, 2000). Acetate has been reported as beneficial for colorectal cancer prevention (Casanova, Azevedo-Silva, Rodrigues, & Preto, 2018;Ferro et al, 2016), while propionate plays an important role in the inhibition of cholesterol synthesis and the deposition of adipose tissue, being proposed as a dietary factor to depress appetite and reduce obesity (Arora, Sharma, & Fros, 2011).…”

Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics and Oncogenesis—Part 1: Acetyl-CoA, Acetogenesis and Acyl-CoA Short-Chain Synthetases

“…Ketone bodies and acetate are transported predominantly by MCT1, MCT2 and to a lesser extent by MCT4, whereas MCT3 is involved in lactate transport. There is also evidence that acetate may be passively transported into or out of some cells through aquaporins (Ferro et al, 2016).…”

In vitro fermentation of raffinose to unravel its potential as prebiotic ingredient

“…Overall, acetate was the main SCFAs accumulated at 48 h (D1: 37.4 ± 0.7 mmol/L blank, 77.5 ± 0.6 mmol/L lactulose and 73.6 ± 1.4 mmol/L rafinose; D2: 30.2 ± 0.9 blank, 81.0 ± 0.7 lactulose and 119.1 ± 0.1 rafinose), with raffinose presenting the highest production of this metabolite that has been reported as playing an important role on colorectal cancer prevention (Casanova, Azevedo-Silva, Rodrigues, & Preto, 2018;Ferro et al, 2016;Oliveira et al, 2015).…”