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S1PR3–G12-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation [MCF-7 RNA-seq]

ABSTRACT: Cancer tissues possess less glucose than surrounding normal tissue, because cancer cells predominantly produce energy by glycolysis than oxidative phosphorylation even in the presence of an adequate oxygen supply (Warburg effect). We found a novel compound ALESIA which causes apoptosis of malignant cells at a low glucose condition from an original phenotypic screening. Identified target molecule of ALESIA was Sphingosine-1-phosphate receptor 3 (S1PR3). Being different from the natural ligand, ALESIA selectively stimulated S1PR3-G12 coupling to S1PR3 without suppression by β-arrestin recruitment and continuously promoted NO synthesis. To reduce the enhanced oxidative stress, NAPDH production through pentose-phosphate pathway and resulting consumption of glucose were promoted in ALESIA-treated cells. ALESIA therefore accelerated glucose starvation of cancer cells and preferentially killed them both in vitro and in vivo.

ORGANISM(S): Homo sapiens

PROVIDER: GSE111352 | GEO | 2021/02/08

REPOSITORIES: GEO

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S1PR3–G12-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation [HeLa RNA-seq]

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S1PR3–G12-biased agonist ALESIA targets cancer metabolism and promotes glucose starvation

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