Galloyl esters of trans-stilbenes are inhibitors of FASN with anticancer activity on non-small cell lung cancer cells

European Journal of Medicinal Chemistry
2019.0

Abstract

Fatty acid synthase (FASN) is a lipogenic enzyme that is selectively upregulated in malignant cells. There is growing consensus on the oncogenicity of FASN-driven lipogenesis and the potential of FASN as a druggable target in cancer. Here, we report the synthesis and FASN inhibitory activities of two novel galloyl esters of trans-stilbene EC1 and EC5. Inhibition of FASN was accompanied by a loss in AKT activation and profound apoptosis in several non-small cell lung cancer (NSCLC) cells at the growth inhibitory concentrations of EC1 and EC5. Both FASN and phospho-AKT levels were concurrently downregulated. However, addition of a lipid concentrate to the treated cells reinstated cell viability and reversed the loss of FASN and AKT protein levels, thus recapitulating the causal relationship between FASN inhibition and the loss in cell viability.

Knowledge Graph

Similar Paper

Galloyl esters of trans-stilbenes are inhibitors of FASN with anticancer activity on non-small cell lung cancer cells
European Journal of Medicinal Chemistry 2019.0
Repositioning Proton Pump Inhibitors as Anticancer Drugs by Targeting the Thioesterase Domain of Human Fatty Acid Synthase
Journal of Medicinal Chemistry 2015.0
Suppression of TNF-α induced NFκB activity by gallic acid and its semi-synthetic esters: possible role in cancer chemoprevention
Natural Product Research 2010.0
Therapeutic Activity of the Lansoprazole Metabolite 5-Hydroxy Lansoprazole Sulfide in Triple-Negative Breast Cancer by Inhibiting the Enoyl Reductase of Fatty Acid Synthase
Journal of Medicinal Chemistry 2022.0
Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase
Journal of Medicinal Chemistry 2008.0
A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids
Bioorganic & Medicinal Chemistry 2017.0
Synthesis and Cytotoxicity Studies of Stilbene Long-Chain Fatty Acid Conjugates
Journal of Natural Products 2020.0
Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2‐overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation
FEBS Letters 2007.0
Antiproliferative activity of synthetic fatty acid amides from renewable resources
Bioorganic & Medicinal Chemistry 2015.0
Acyl derivatives of boswellic acids as inhibitors of NF-κB and STATs
Bioorganic & Medicinal Chemistry Letters 2012.0