In vitro inhibition of prostaglandin biosynthesis in squamous cell carcinoma by retinoids.
The aim of this study was to evaluate the effect of four natural and synthetic retinoids: Ro 12-7310 (I), Ro 13-7410 (II), 13-cis-retinoic acid (III), and Ro 13-7652 (IV) on the synthesis of PGE2 in human squamous cell carcinoma (SCC) of the tongue (SCC-25). 5 X 10(6) cells were plated and labeled with 0.2 microCi of (14C)-arachidonic acid (AA) in 2 ml of DMEM/F12 containing 0.1% BSA for 4 h. The cells were then washed, and incubated in serum-free medium with the retinoids (10,20,30,40 microM) for 1 h. The cells were further stimulated with melittin an additional hour. Radioactive metabolites released in media were then extracted with diethyl ether. The ether extracts were separated by TLC and radioactive PGE2 zone was quantitated by means of liquid scintillation counting. The rank order of percent inhibition of PGE2 synthesis by retinoids at four concentration levels was (I) greater than (II) greater than (III) greater than (IV). Since inhibition of PG production has been demonstrated to suppress growth of tumors in animal models and humans, further study on the effect of retinoids on growth of SCC in vitro as well as in vivo seems warranted.
elAttar
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Laboratory of Hormone Research, School of Dentistry, University of Missouri, Kansas City 64108.
Lin
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D017255:Acitretin; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005050:Etretinate / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012176:Retinoids / Q000008:administration & dosage / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000378:metabolism*; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D001565:Benzoates; D012176:Retinoids; D016718:Arachidonic Acid; D014212:Tretinoin; C066048:Ro 12-7310; D005050:Etretinate; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D017255:Acitretin