1 research outputs found
A Fluorescence-Based Assay to Probe Inhibitory Effect of Fructose Mimics on GLUT5 Transport in Breast Cancer Cells
Rapid cell division
and reprogramming of energy metabolism are
two crucial hallmarks of cancer cells. In humans, hexose trafficking
into cancer cells is mainly mediated through a family of glucose transporters
(GLUTs), which are facilitative transmembrane hexose transporter proteins.
In several breast cancers, fructose can functionally substitute glucose
as an alternative energy supply supporting rapid proliferation. GLUT5,
the principal fructose transporter, is overexpressed in human breast
cancer cells, providing valuable targets for breast cancer detection
as well as selective targeting of anticancer drugs using structurally
modified fructose mimics. Herein, a novel fluorescence assay was designed
aiming to screen a series of C-3 modified 2,5-anhydromannitol (2,5-AM)
compounds as d-fructose analogues to explore GLUT5 binding
site requirements. The synthesized probes were evaluated for their
ability to inhibit the uptake of the fluorescently labeled d-fructose derivative 6-NBDF into EMT6 murine breast cancer cells.
A few of the compounds screened demonstrated highly potent single-digit
micromolar inhibition of 6-NBDF cellular uptake, which was substantially
more potent than the natural substrate d-fructose, at a level
of 100-fold or more. The results of this assay are consistent with
those obtained from a previous study conducted for some selected compounds
against 18F-labeled d-fructose-based probe 6-[18F]FDF, indicating the reproducibility of the current non-radiolabeled
assay. These highly potent compounds assessed against 6-NBDF open
avenues for the development of more potent probes targeting GLUT5-expressing
cancerous cells