Anti-cancer strategy targeting the energy metabolism of tumor cells surviving a low-nutrient acidic microenvironment.

ABSTRACT:

Objective

Tumor cells experience hypoxia, acidosis, and hypoglycemia. Metabolic adaptation to glucose shortage is essential to maintain tumor cells' survival because of their high glucose requirement. This study evaluated the hypothesis that acidosis might promote tumor survival during glucose shortage and if so, explored a novel drug targeting metabolic vulnerability to glucose shortage.

Methods

Cell survival and bioenergetics metabolism were assessed in lung cancer cell lines. Our in-house small-molecule compounds were screened to identify those that kill cancer cells under low-glucose conditions. Cytotoxicity against non-cancerous cells was also assessed. Tumor growth was evaluated in vivo using a mouse engraft model.

Results

Acidosis limited the cellular consumpti

SUBMITTER: Maeda Y 

PROVIDER: S-EPMC7578269 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature