Antitumor Effects of Orally Administered Rare Sugar D-Allose in Bladder Cancer

International Journal of Molecular Sciences

Emi Ibuki¹  Reiji Haba¹  Mikio Sugimoto²  Xia Zhang²  Yoshiyuki Kakehi²  Yoichiro Tohi²  Yuki Matsuoka²  Rikiya Taoka²  Akihide Yoshihara³  Ken Izumori³  Kazuya Akimitsu³ 

[1] Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho 761-0793, Japan;Department of Urology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho 761-0793, Japan;International Institute of Rare Sugar Research and Education, Kagawa University, 2393 Ikenobe, Miki-cho 761-0795, Japan;

关键词: bladder cancer;    D-allose;    rare sugar;    reactive oxygen species;    thioredoxin-interacting protein;   

DOI  :  10.3390/ijms23126771

来源: DOAJ

【 摘 要 】

D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (TXNIP) expression and affect the production of intracellular reactive oxygen species (ROS). However, the antitumor effect of D-allose is unknown. This study aimed to determine whether orally administered D-allose could be a candidate drug against bladder cancer (BC). To this end, BC cell lines were treated with varying concentrations of D-allose (10, 25, and 50 mM). Cell viability and intracellular ROS levels were assessed using cell viability assay and flow cytometry. TXNIP expression was evaluated using Western blotting. The antitumor effect of orally administered D-allose was assessed using a xenograft mouse model. D-allose reduced cell viability and induced intracellular ROS production in BC cells. Moreover, D-allose stimulated TXNIP expression in a dose-dependent manner. Co-treatment of D-allose and the antioxidant L-glutathione canceled the D-allose-induced reduction in cell viability and intracellular ROS elevation. Furthermore, oral administration of D-allose inhibited tumor growth without adverse effects (p < 0.05). Histopathological findings in tumor tissues showed that D-allose decreased the nuclear fission rate from 4.1 to 1.1% (p = 0.004). Oral administration of D-allose suppressed BC growth in a preclinical mouse model, possibly through up-regulation of TXNIP expression followed by an increase in intracellular ROS. Therefore, D-allose is a potential therapeutic compound for the treatment of BC.

【 授权许可】

Unknown