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.
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Authors | Yu-Jia Tan, Azhar Ali, Sheng-Yang Tee, Jun-Ting Teo, Yu Xi, Mei-Lin Go, Yulin Lam |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 182
Pg. 111597
(Nov 15 2019)
ISSN: 1768-3254 [Electronic] France |
PMID | 31422225
(Publication Type: Journal Article)
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Copyright | Copyright © 2019 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Esters
- Stilbenes
- Gallic Acid
- FASN protein, human
- Fatty Acid Synthase, Type I
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Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, metabolism, pathology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Esters
(chemical synthesis, chemistry, pharmacology)
- Fatty Acid Synthase, Type I
(antagonists & inhibitors, metabolism)
- Gallic Acid
(analogs & derivatives, chemistry, pharmacology)
- Humans
- Lung Neoplasms
(drug therapy, metabolism, pathology)
- Molecular Structure
- Stilbenes
(chemical synthesis, chemistry, pharmacology)
- Structure-Activity Relationship
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