Abstract
Objectives
Our main aim is to test the effect of estrogen and antiestrogen (letrozole) on the modulation of fatty acid desaturation and ScA levels in vitro using human cancer cells.
Methods
We used two sets of cells, MCF7 cells stably expressing FADS1 and FADS2 genes and a series of wild type (MCF7, HepG2, SK-N-SH, Caco2 and Y79) cancer cells. Cells were treated with estrogen (0 to 200 ppm) or letrozole (0 to 100 ppm) at the time of seeding and at confluence 50 μM albumin bound 20:2n-6 was added to FBS-free media. FAME was quantified by GC-flame ionization detector (GC-FID) and structures were identified by gas chromatography (GC) – covalent adduct chemical ionization mass spectrometry (CACI-MS/MS).
Results
Estrogen caused a dose dependent decrease in ScA via apparent inhibition of FADS1 activity in all wild type and had no effect on FADS2 (Δ8 desaturation) mediated synthesis of DGLA. In MCF7 cells, letrozole caused a dose dependent increase in FADS2 catalyzed DGLA and a decrease in ScA.
Conclusions
We provide the first biochemical evidence demonstrating MCF7 cells treated with letrozole increase DGLA, the immediate precursor to the anti-inflammatory eicosanoid PGE1. Letrozole is the first hormone-active agent to have opposing effects on FADS1 and FADS2.
Funding Sources
NIH grant R01 AT007003.
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