The Marine-Derived Fungus Clonostachys rosea, Source of a Rare Conjugated 4-Me-6E,8E-hexadecadienoic Acid Reducing Viability of MCF-7 Breast Cancer Cells and Gene Expression of Lipogenic Enzymes

Mar Drugs. 2015 Aug 6;13(8):4934-48. doi: 10.3390/md13084934.

Abstract

A marine-derived strain of Clonostachys rosea isolated from sediments of the river Loire estuary (France) was investigated for its high lipid production. The fungal strain was grown on six different culture media to explore lipid production changes. An original branched conjugated fatty acid, mainly present in triglycerides and mostly produced when grown on DCA (23% of total fatty acid composition). It was identified as 4-Me-6E,8E-hexadecadienoic on the basis of spectroscopic analyses. This fatty acid reduced viability of MCF-7 breast cancer cells in a dose dependent manner (up to 63%) at physiological free fatty acid human plasma concentration (100 μM). Reduction of gene expression of two lipogenic enzymes, the acetyl CoA carboxylase (ACC) and the fatty acid synthase (FAS) was evaluated to explore the mechanisms of action of 4-Me-6E,8E-16:2 acid. At 50 μM, 50% and 35% of mRNA gene expression inhibition were observed for ACC and FAS, respectively.

Keywords: Clonostachys rosea; MCF-7; acetyl-CoA carboxylase; anti-carcinogenic; cancer; conjugated fatty acid; fatty acid synthase; fatty acids; lipids; lipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Aquatic Organisms / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • Cell Survival / genetics
  • Fatty Acid Synthases / genetics
  • Fatty Acids / genetics
  • Female
  • France
  • Fungi / metabolism*
  • Gene Expression / drug effects*
  • Gene Expression / genetics
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Enzymologic / genetics
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • MCF-7 Cells
  • RNA, Messenger / genetics
  • Triglycerides / genetics

Substances

  • Fatty Acids
  • RNA, Messenger
  • Triglycerides
  • Fatty Acid Synthases
  • Acetyl-CoA Carboxylase