Inhibition of bladder cancer cell proliferation by 2-deoxy-D-glucose: A potential therapeutic approach

Abstract

BackgroundBladder cancer cells exhibit a high dependency on glycolysis for energy production and survival. 2-Deoxy-D-glucose (2-DG), a glucose analog, inhibits glycolysis by targeting hexokinase, leading to energy depletion and growth suppression in cancer cells. ObjectiveThis study investigated the effects of 2-DG on proliferation, glycolytic activity, oxidative stress, and apoptosis in human bladder cancer cells to evaluate its potential as a therapeutic agent. MethodsFive human bladder cancer cell lines (RT112, 253J, T24, HT1197 and J82) were treated with increasing concentrations of 2-DG (0-20 mM) for up to 72 h. Cell viability was assessed by MTT assay, and glycolytic activity was evaluated by measuring hexokinase (HK) activity and intracellular ATP levels. Reactive oxygen species (ROS) production and apoptosis were analyzed by flow cytometry, and in vivo efficacy was examined using xenograft models in nude mice. All experiments were performed in triplicate. Results2-DG significantly reduced cell viability in a dose-dependent manner across all cell lines, concomitant with decreased HK activity and ATP production (p < 0.05). Treatment induced ROS accumulation and apoptosis, as evidenced by increased cleaved PARP and Bax expression and decreased p-Akt and Bcl-2 levels. In xenograft models, 2-DG treatment markedly suppressed tumor growth without apparent systemic toxicity. Conclusions2-DG exerts potent antitumor effects against bladder cancer by inhibiting glycolysis, inducing oxidative stress, and activating apoptotic pathways. These findings support the therapeutic potential of 2-DG as a metabolic-targeting strategy for bladder cancer.