D-Allose Inhibits Cancer Cell Growth by Reducing GLUTI Expression

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28745
Title
D-Allose Inhibits Cancer Cell Growth by Reducing GLUTI Expression
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Description

Abstract

Glucose is a major energy source for mammalian cells and is transported into cells via cell-specific expression of various glucose transporters (GLUTs). Especially, cancer cells require massive amounts of glucose as an energy source for their dysregulated growth and thus over-express GLUTs. d-allose, a C-3 epimer of d-glucose, is one of rare sugars that exist in small quantities in nature. We have shown that d-allose induces the tumor suppressor gene coding for thioredoxin interacting protein (TXNIP) and inhibits cancer cell growth by G1 cell cycle arrest. It has also been reported that GLUTs including GLUT1 are over-expressed in many cancer cell lines, which may contribute to larger glucose utilization. Since d-allose suppresses the growth of cancer cells through the upregulation of TXNIP expression, our present study focused on whether d-allose down-regulates GLUT1 expression via TXNIP expression and thus suppresses cancer cell growth. Western blot and real-time PCR analyses revealed that d-allose significantly induced TXNIP expression and inhibited GLUT1 expression in a dose-dependent manner in three human cancer cell lines: hepatocellular carcinoma (HuH-7), Caucasian breast adenocarcinoma (MDA-MB-231), and neuroblastoma (SH-SY5Y). In these cell lines, d-allose treatment inhibited cell growth. Importantly, d-allose treatment decreased glucose uptake, as measured by the uptake of 2-deoxy d-glucose. Moreover, the reporter assays showed that d-allose decreased the expression of luciferase through the hypoxia response element present in the tested promoter region. These results suggest that d-allose may cause the inhibition of cancer growth by reducing both GLUT1 expression and glucose uptake.

Keywords: D-allose, glucose transporter 1, hypoxia response element, rare sugar, thioredoxin interacting protein

(医博甲627)

Author
著者 野口 知里
著者(ヨミ) ノグチ チサト
著者(別表記) Noguchi Chisato
Publication Title
Tohoku Journal of Experimental Medicine
Publication Title Alternative
Tohoku J Exp Med.
Volume
238
Issue
2
Start Page
131
End Page
141
Publisher
Tohoky University Medical Press
東北ジャーナル刊行会
Published Date
2016-02
ISSN
0040-8727
NCID
AA00863920
PMID
26829886
DOI
10.1620/tjem.238.131
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.1620/tjem.238.131
Rights
Copyright © 2016 Tohoku University Medical Press
"This is the Publisher's version of the following article: D-Allose Inhibits Cancer Cell Growth by Reducing GLUTI Expression; Tohoku Journal of Experimental Medicine ; Volume 238 Issue 2 (2016) Pages: 131-141; doi: 10.1620/tjem.238.131, which has been published in final form at https://doi.org/10.1620/tjem.238.131 . "
Text Version
ETD
Grant ID
博甲第627号
Grant Date
2016-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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