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
Ana Camila Dos Santos Dias,
Nicolas Ruiz,
Aurélie Couzinet-Mossion,
Samuel Bertrand,
Muriel Duflos,
Yves-François Pouchus,
Gilles Barnathan,
Hassan Nazih,
Gaetane Wielgosz-Collin
Affiliations
Ana Camila Dos Santos Dias
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
Nicolas Ruiz
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
Aurélie Couzinet-Mossion
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
Samuel Bertrand
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
Muriel Duflos
Faculty of Pharmacy, University of Nantes, IICiMed, 9 Rue Bias, 44000 Nantes, France
Yves-François Pouchus
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
Gilles Barnathan
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
Hassan Nazih
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
Gaetane Wielgosz-Collin
Faculty of Pharmacy, University of Nantes, MMS; 9, Rue Bias, 44000 Nantes, France
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.