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

Suellen Ferro1,2, João Azevedo-Silva1, Margarida Casal1

  • 1CBMA- Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, Braga, Portugal.

Oncotarget
|September 7, 2017
PubMed

Insights

Acetate enters colorectal cancer (CRC) cells via specific transporters, influencing their metabolism and enhancing apoptosis. Combining acetate with 3-bromopyruvate (3BP) shows potential for CRC therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Short-chain fatty acids, including acetate, are linked to colorectal cancer (CRC) prevention and therapy.
  • Acetate has demonstrated the ability to induce apoptosis in CRC cells.
  • The exact mechanisms of acetate transport in CRC cells and its role in CRC metabolism require further elucidation.

Purpose of the Study:

  • To investigate the mechanisms of acetate transport across colorectal cancer cell membranes.
  • To assess the impact of acetate on CRC glycolytic metabolism.
  • To explore the combined therapeutic potential of acetate and 3-bromopyruvate (3BP) in CRC.

Main Methods:

  • Investigated acetate transport using secondary active transporters (MCT1, MCT2, SMCT1) and facilitated diffusion via aquaporins.
  • Analyzed the effect of acetate on CRC cell expression of MCT1, MCT4, and CD147.
  • Assessed acetate's influence on CRC cell glycolysis and apoptosis, including combination therapy with 3BP.

Main Results:

  • Acetate enters CRC cells via MCT1/MCT2, SMCT1, and aquaporins.
  • Acetate exposure upregulates MCT1, MCT4, and CD147 expression and promotes MCT1 plasma membrane localization in CRC cells.
  • Acetate enhances CRC cell glycolysis, and its apoptosis-inducing and anti-proliferative effects are potentiated by 3BP.

Conclusions:

  • Acetate transport mechanisms, including aquaporins and MCTs, are likely involved in its selectivity towards CRC cells due to their overexpression in clinical cases.
  • Acetate influences CRC cell metabolism and apoptosis, suggesting a role in CRC therapy.
  • Targeting acetate transport, in combination with glycolytic inhibitors like 3BP, represents a promising therapeutic strategy for colorectal cancer.

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