2. Academic Validation
  3. Galloyl esters of trans-stilbenes are inhibitors of FASN with anticancer activity on non-small cell lung cancer cells

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

  • Eur J Med Chem. 2019 Nov 15:182:111597. doi: 10.1016/j.ejmech.2019.111597.
Yu-Jia Tan 1,  Azhar Ali 2,  Sheng-Yang Tee 1,  Jun-Ting Teo 2,  Yu Xi 3,  Mei-Lin Go 4,  Yulin Lam 1
Affiliations

Affiliations

  • 1 Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore.
  • 2 Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, 14 Medical Drive, 117599, Singapore.
  • 3 Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore.
  • 4 Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore. Electronic address: meilin.go@nus.edu.sg.
PMID: 31422225 DOI: 10.1016/j.ejmech.2019.111597
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.

Keywords

Anticancer; EGCG; FASN inhibitors; Galloyl esters of trans-stilbenes; Non-small cell lung cancer.

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