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Fatty Acid Suppression of Cell Proliferation is Associated with the Inhibition of Polyisoprenylated Methylated Protein Methyl Esterase
Author(s) -
Amissah Felix,
Taylor Shalina,
Duverna Randolph,
Lamango Nazarius S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.503.1
Subject(s) - arachidonic acid , chemistry , esterase , viability assay , biochemistry , cell growth , prostaglandin , polyunsaturated fatty acid , lauric acid , cell , microsome , fatty acid , enzyme , pharmacology , biology
Protein polyisoprenylation is essential for the activities of oncogenic proteins such as Ras. The final, reversible step of polyisoprenylation pathway is catalyzed by an ester forming polyisoprenylated protein methyl transferase and polyisoprenylated methylated protein methyl esterase (PMPMEase). Various free fatty acids (FFAs) were analyzed to test whether their beneficial health effects are associated with PMPMEase inhibition. The potent inhibitory FFAs were further analyzed for their effects on cell viability. Arachidonic acid (AA) and lauric acid (LA) inhibited PMPMEase with 0.19 and 6.5 ìM, respectively. AA was over 63‐fold more inhibitory than Prostaglandin A2 (Ki of 12 ìM) while prostaglandin E2 and long chain saturated fatty acids were not inhibitory even at 1 mM. AA and LA inhibited the viability of human neuroblastoma cells with EC50 values of 11 and 25 ìM respectively, after 72 h exposure. Therefore AA and other PUFAs may be involved in the regulation of cell proliferation and that the elevated levels of COX‐2 in tumors convert PUFAs which inhibit PMPMEase at physiological concentrations, to prostanoids that are ineffective at inhibiting both PMPMEase and thus cell proliferation. NSAIDs may thus owe their anticancer effects through their ability to protect the PMPMEase‐ and cell proliferation‐inhibiting PUFAs from COX‐2 metabolism. Grant Funding Source : NIH/NIGMS/SCORE (GM 08111‐35) & NIH/NCRR (G12 RR0 3020)