Inhibition of fatty acid transport and proliferative activity in tissue-isolated human squamous cell cancer xenografts perfused in situ with melatonin or eicosapentaenoic or conjugated linoleic acids.
Melatonin and eicosapentaenoic and 10t,12c-conjugated linoleic acids suppress the growth-stimulating effects of linoleic acid (LA) and its metabolism to the mitogenic agent 13-(S)-hydroxyoctadecadienoic acid (13-(S)-HODE) in established rodent tumors and human cancer xenografts. Here we compared the effects of these 3 inhibitory agents on growth and LA uptake and metabolism in human FaDu squamous cell carcinoma xenografts perfused in situ in male nude rats. Results demonstrated that these agents caused rapid inhibition of LA uptake, tumor cAMP content, 13-(S)-HODE formation, extracellular signal-regulated kinase p44/ p42 (ERK 1/2) activity, mitogen-activated protein kinase kinase (MEK) activity, and [3H]thymidine incorporation into tumor DNA. Melatonin's inhibitory effects were reversible with either the melatonin receptor antagonist S20928, pertussis toxin, forskolin, or 8-bromoadenosine-cAMP, suggesting that its growth-inhibitory effect occurs in vivo via a receptor-mediated, pertussis-toxin-sensitive pathway.
Dauchy
Robert T
RT
Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, NY, USA. robert.dauchy@bassett.org
Dauchy
Erin M
EM
Davidson
Leslie K
LK
Krause
Jean A
JA
Lynch
Darin T
DT
Tirrell
Paul C
PC
Tirrell
Robert P
RP
Sauer
Leonard A
LA
Van der Riet
Peter
P
Blask
David E
DE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D008041:Linoleic Acids / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D011915:Rats, Inbred BUF; D011923:Rats, Nude; D023041:Xenograft Model Antitumor Assays