Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2.

ABSTRACT:

Background

Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy.

Methods

Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity. Enzyme inhibition, cytotoxicity, apoptosis, intracellular ATP level, mitochondrial membrane potential (MMP), glucose uptake and lactate production experiments were undertaken in SW480 cells to identify Benz as a HK2 inhibitor. Western blot was used to test protein express

SUBMITTER: Li W 

PROVIDER: S-EPMC5399312 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature