In vitro and in vivo effects of D-allose: up-regulation of thioredoxin-interacting protein in head and neck cancer cells.
OBJECTIVE
This study was aimed to investigate the relationship between the antiproliferative effects of D-allose and the up-regulation of thioredoxin-interacting protein (TXNIP) in head and neck cancer cells.


METHODS
For the in vitro study, 5 oral squamous cell carcinoma cell lines (Ca9-22, HSC-3, HSC-4, SAS, and KON) were treated with 25 mmol/L D-allose. For the in vivo study, HSC-3 cells were used in a xenograft model with female athymic nude mice (BALB/c nu/nu; 5 to 6 weeks old).


RESULTS
Inhibition of cell growth by D-allose was noted in HSC-3 and Ca9-22 cells, along with significant induction of TXNIP. Although TXNIP up-regulation was also evident, albeit to a lesser extent, in the remaining cell lines, D-allose did not inhibit their growth. With the HSC-3 line, the cell survival fractions decreased and TXNIP expression increased in a D-allose dose-dependent manner. The antiproliferative effects were partially suppressed by concomitant D-glucose treatment, which also reduced TXNIP expression. In the in vivo experiment, the tumor volume at day 15 after D-allose treatment was reduced to 61% of that of the control group.


CONCLUSIONS
This study showed that D-allose exerts growth inhibitory effects on head and neck cancer cells in vitro and in vivo. The sugar may act as an antiproliferative agent via TXNIP induction and thus may be useful as a novel anticancer drug.
Hoshikawa
Hiroshi
H
Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kita, Japan.
Mori
Terushige
T
Mori
Nozomu
N
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013879:Thioredoxins / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D002352:Carrier Proteins; C486715:TXNIP protein, human; D013879:Thioredoxins; C002055:allose; D005947:Glucose