D-Allose Inhibits Cancer Cell Growth by Reducing GLUT1 Expression
| Autor: | Masaaki Tokuda, Fuminori Yamaguchi, Li Sui, Akram Hossain, Youyi Dong, Kazuyo Kamitori, Chisato Noguchi, Hiroshi Hoshikawa, Ayako Katagi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Thioredoxin-Interacting Protein Glucose uptake Down-Regulation Biology Response Elements General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cell Line Tumor Neoplasms medicine Humans RNA Messenger Cell Proliferation Glucose Transporter Type 1 Cell growth Glucose transporter Cancer General Medicine medicine.disease Molecular biology Up-Regulation Gene Expression Regulation Neoplastic Glucose 030104 developmental biology Gene Knockdown Techniques Cancer cell Cancer research biology.protein GLUT1 Carrier Proteins TXNIP |
| Zdroj: | The Tohoku Journal of Experimental Medicine. 238:131-141 |
| ISSN: | 1349-3329 0040-8727 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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