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.

Bladder cancer is characterized by metabolic reprogramming, and enhanced glycolysis contributes to tumor progression and therapeutic resistance. Because the anticancer activity of 2-Deoxy-d-glucose (2-DG) has been reported in several malignancies, this study evaluated the antiproliferative and metabolism-modulating effects of 2-DG and their association with oxidative stress-related signaling in bladder cancer models. Human bladder cancer cell lines were examined using MTT assays, hexokinase (HK) activity assays, ATP measurements, DCF-DA-based reactive oxygen species (ROS) analysis, and Western blotting. RT112 and 253J cells were selected for mechanistic analyses, and the antitumor efficacy of 2-DG was further evaluated in xenograft models. Treatment with 2-DG reduced the metabolic activity of all five bladder cancer cell lines in a concentration-dependent manner and was associated with decreased HK activity and intracellular ATP levels. Increased ROS-sensitive fluorescence was accompanied by upregulation of TXNIP and BAX and downregulation of AKT and BCL-2, indicating a shift toward a pro-apoptotic pattern of apoptosis-related protein expression. In vivo, systemic administration of 2-DG significantly suppressed xenograft tumor growth without apparent body weight loss or histological abnormalities in the liver or kidneys. These findings suggest that 2-DG suppresses bladder cancer growth in association with metabolic disruption, increased ROS-sensitive fluorescence, TXNIP/AKT-related changes, and modulation of BAX/BCL-2 expression. However, additional studies are required to clarify the underlying mechanisms and further evaluate its safety profile.

Enhydrin, a melampolide-type sesquiterpene lactone abundant in the leaves of yacon (Smallanthus sonchifolius), has not previously been investigated for its anti-prostate cancer activity. This study investigated the antiproliferative effects of enhydrin in human prostate cancer cells, its regulatory effects on apoptosis-related molecules, and its impact on the PI3K/AKT and NF-κB signaling pathways. Three prostate cancer cell lines (PC3, DU145, and LNCaP) were treated with enhydrin, and its effects were analyzed using cell viability assays, morphological observation, flow cytometry, apoptosis-focused TaqMan qPCR array, qRT-PCR, and Western blotting. In vivo antitumor activity was assessed in a PC3 xenograft mouse model. Enhydrin reduced cell viability in a dose- and time-dependent manner, induced morphological changes associated with cytotoxicity, and caused G1 cell-cycle arrest. Gene expression analysis revealed downregulation of PI3K/AKT- and NF-κB-related genes and modulation of BCL2 family genes toward a pro-apoptotic profile, which was confirmed at both mRNA and protein levels. In vivo, enhydrin suppressed tumor growth without significant body-weight loss. These findings suggest that enhydrin exerts antitumor effects in prostate cancer by reducing the expression of PI3K/AKT and NF-κB related molecules and modulating apoptosis-related proteins. Although additional studies are required to determine pathway activity, directly confirm apoptosis, and evaluate normal-cell cytotoxicity and the therapeutic window, these findings provide preliminary biological evidence of the effects of enhydrin in prostate cancer models.