Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo biloba and their cytotoxic activity

J Enzyme Inhib Med Chem. 2013 Jun;28(3):565-8. doi: 10.3109/14756366.2012.658786. Epub 2012 Mar 1.

Abstract

Fatty acid synthase (FAS) has been proposed to be a new drug target for the development of anticancer agents because of the significant difference in expression of FAS between normal and tumour cells. Since a n-hexane-soluble extract from Ginkgo biloba was demonstrated to inhibit FAS activity in our preliminary test, we isolated active compounds from the n-hexane-soluble extract and evaluated their cytotoxic activity in human cancer cells. Three ginkgolic acids 1-3 isolated from the n-hexane-soluble extract inhibited the enzyme with IC(50) values 17.1, 9.2 and 10.5 µM, respectively, and they showed cytotoxic activity against MCF-7 (human breast adenocarcinoma), A549 (human lung adenocarcinoma) and HL-60 (human leukaemia) cells. Our findings suggest that alkylphenol derivatives might be a new type of FAS inhibitor with cytotoxic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acid Synthases / antagonists & inhibitors*
  • Female
  • Ginkgo biloba / chemistry*
  • HL-60 Cells / drug effects
  • Hexanes / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Salicylates / chemistry
  • Salicylates / isolation & purification
  • Salicylates / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Hexanes
  • Plant Extracts
  • Salicylates
  • ginkgolic acid
  • n-hexane
  • Fatty Acid Synthases