Abstract
Scope:
Metabolic disorder is a pivotal hallmark of cancer cells. Sulforaphane (SFN) is reported to improve lipid metabolism. However, the effect of SFN on glucose metabolism in bladder cancer remains unclear. Hence, we investigated the effect and underling mechanism.
Methods and results:
We collected biological samples from bladder cancer patients, and also investigated using N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder cancer mice and bladder cancer cell lines. A novel glucose transport aberrant-independent aerobic glycolysis was found in bladder cancer patients, and the lower malignancy tissues have the more obvious abnormality. SFN strongly down-regulated ATP production by inhibiting glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). Both in vitro cell culture and in bladder tumor mice, SFN weakened the glycolytic flux by suppressing multiple metabolic enzymes, including hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH). Moreover, SFN decreased the level of AKT1 and p-AKT ser473 , especially in low-invasive UMUC3 cells. The down-regulation of ATP and HK2 by SFN were both reversed by AKT1 overexpression.
Conclusions:
SFN down-regulated the unique glucose transport aberrant-independent aerobic glycolysis existed in bladder cancer via blocking the AKT1/HK2 axis and PDH expression. This article is protected by copyright. All rights reserved.
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