Blockade of fructose transporter protein GLUT5 inhibits proliferation of colon cancer cells: proof of concept for a new class of anti-tumor therapeutics

Pharmacol Rep. 2021 Jun;73(3):939-945. doi: 10.1007/s43440-021-00281-9. Epub 2021 May 29.

Abstract

Background: Despite the fact that colorectal cancer (CRC) is one of the most commonly diagnosed cancers in men and women, its current treatment remains unsatisfactory and therefore novel studies proposing new approaches are necessary. A high sugar diet is believed to promote carcinogenesis. Fructose is absorbed from the gastrointestinal tract by members of the glucose transporter family-GLUT. The aim of the study was to characterize the expression of GLUT5 at mRNA level in CRC patients. Moreover, our goal was to elucidate the molecular role of GLUT5 in CRC and assess whether GLUT5 inhibitor may affect the viability of colon cancer cells.

Methods: The expression of GLUT5 at mRNA level was characterized based on 30 samples from resected colorectal cancers and 30 healthy colonic mucosa specimens from surgical margins. The inhibitory effect of N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine (MSBNA) was assessed on a colon cancer cell line, HT-29, and normal colon epithelium cells-CCD 841 CoN Cells.

Results: GLUT5 expression was found in 96.7% of cancer specimens and only in 53.3% of healthy mucosa fragments. In cancer tissue, real-time PCR analysis showed almost 2, fivefold (p< 0.001) increase of GLUT5 mRNA expression level compared with the healthy intestinal mucosa. GLUT5 inhibitor, MSNBA (10 µM) significantly decreased the viability of colon cancer cells, while barely affected the viability of normal colon epithelium cells.

Conclusions: Our study suggests that a strong focus should be put on GLUT5 and its inhibitors for both diagnostic and therapeutic purposes in CRC.

Keywords: Colorectal cancer; Fructose; GLUT5; N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Colon / drug effects
  • Colon / metabolism
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism*
  • Female
  • Fructose / metabolism*
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Glucose Transporter Type 5 / antagonists & inhibitors*
  • HT29 Cells
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Messenger / metabolism

Substances

  • Antineoplastic Agents
  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 5
  • RNA, Messenger
  • SLC2A5 protein, human
  • Fructose