D-Allose Inhibits Cancer Cell Growth by Reducing GLUT1 Expression

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 overexpressed 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.

<p>LncRNA-SNHG16 Silencing Inhibits Prostate Carcinoma Cell Growth, Downregulate GLUT1 Expression and Reduce Glucose Uptake</p>

“…GLUT1 is a major player in glucose metabolism in cancer biology, which is usually up-regulated in different types of cancers. 16 Overexpression of GLUT1 not only accelerated glucose metabolism but also protected cancer cells from glucose deprivation-induced oxidative stress. 17 GLUT1 expression inhibition is considered to be a therapeutic target for cancer treatment.…”

Additive antitumour effect of D‑allose in combination with cisplatin in non-small cell lung cancer cells

“…Third, apoptosis could be induced by D-allose (7), however, apoptosis may not appear in all types of cells (3). Fourth, D-allose can inhibit glucose transporter expression and glucose uptake in several human cancer cell lines (9). Some of the above mechanisms of the antitumour effect of D-allose could be associated with regulating expression of thioredoxin and TXNIP, that is, redox status in the broader sense.…”

“…Recent studies have shown that D-allose has growth inhibitory effects in several kinds of malignancies including hepatocellular carcinoma, prostate, ovarian, and head and neck cancers, and leukaemia (3)(4)(5)(6)(7)(8)(9). However, the effect of D-allose on lung cancer progression has not been studied.…”

“…Notably, TXNIP deficiency initiated hepatocellular carcinogenesis in transgenic mice (20). In addition, recent reports have shown that D-allose stimulates the expression of TXNIP in several kinds of malignancy (7,9,21,22).…”

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

“…This compound, a C-3 epimer of d-glucose with 80% of the sweetness of sucrose, exists in small quantities in nature. This compound is known to possess anticarcinogenic properties via upregulation of thioredoxin interacting protein (TXNIP) [166]. A study involving breast adenocarcinoma, hepatocellular carcinoma, and neuroblastoma cell lines concluded that d-allose downregulates GLUT1 expression and consequently glucose uptake, thus suppressing cancer cell growth, as a result of overexpression of TXNIP [166] (Table 3).…”