Differential modulation of malignant peripheral nerve sheath tumor growth by omega-3 and omega-6 fatty acids.
Neurofibromatosis type 1 (NF1) is a common genetic disorder of the nervous system resulting in neurofibromas and malignant peripheral nerve sheath tumors (MPNST). In this study, we report the modulation of murine and human MPNST cell growth by the fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA demonstrated a tendency to stimulate cell growth at low doses and induce apoptosis at high doses, paralleled by the activation of ERK and caspase-3. Furthermore, high-dose DHA reversed the stimulation of MPNST cell growth by a number of growth factors suggested to have a pathogenic effect in NF1 and inhibited MPNST growth in vivo. AA was found to have a reciprocal activity in vitro, stimulating MPNST cell growth at comparable concentrations and reducing DHA activation of ERK. These findings introduce fatty acids as a possible regulator of MPNST development in NF1 patients.
Mashour
George A
GA
Molecular Neurosurgery Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Drissel
Stephanie N
SN
Frahm
Silke
S
Farassati
Faris
F
Martuza
Robert L
RL
Mautner
Victor-F
VF
Kindler-Röhrborn
Andrea
A
Kurtz
Andreas
A
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018317:Nerve Sheath Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D020928:Mitogen-Activated Protein Kinases