Suppressive effects of novel ferulic acid derivatives on cellular responses induced by phorbol ester, and by combined lipopolysaccharide and interferon-gamma.
A total of 23 ferulic acid (FA) derivatives were synthesized, and investigated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus (EBV) activation and superoxide (O(2)(-)) generation. Most of the derivatives showed significant EBV activation suppression or cytotoxicity at a concentration of 100 microM, with FA15 as the most potent suppressor. In both assays, FA6-FA17, bearing straight- or branched-alkyl side chains, exhibited marked suppression of O(2)(-) generation, with both FA16 and FA17 being highly active, while FA itself was virtually inactive. The activity differences seen between FA16/FA17 and FA are attributable, at least in part, to their cellular incorporating efficiencies. Further, both FA15 and FA21 attenuated the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins, while FA did not. Our results suggest that these novel FA derivatives are effective chemopreventive agents.
Murakami
A
A
Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita, Wakayama, Japan.
Kadota
M
M
Takahashi
D
D
Taniguchi
H
H
Nomura
E
E
Hosoda
A
A
Tsuno
T
T
Maruta
Y
Y
Ohigashi
H
H
Koshimizu
K
K
D000818:Animals; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D003373:Coumaric Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects
D016588:Anticarcinogenic Agents; D003373:Coumaric Acids; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D013481:Superoxides; D007371:Interferon-gamma; C004999:ferulic acid; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate