Inducer-specific bidirectional regulation by thalidomide and phenylphthalimides of tumor necrosis factor-alpha production.
Regulation by thalidomide [N(alpha)-phthalimidoglutarimide] of tumor necrosis factor (TNF)-alpha production was found to be inducer-specific. Thalidomide enhances TNF-alpha production by human leukemia HL-60 cells induced with 12-O-tetradecanoylphorbol 13-acetate (TPA), while it inhibits TNF-alpha production induced with okadaic acid (OA) in the same cell line. Some phthalimide analogs, included PP-33 [2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione] and its 4,5,6,7-tetrafluora derivative FPP-33), also showed such an inducer-specific bidirectional TNF-alpha production-regulating activity. The structure-activity relationships of the compounds tested are similar, but not identical, in the TPA-stimulated HL-60 and OA-stimulated HL-60 assay systems.
Miyachi
H
H
Institute of Molecular and Cellular Biosciences, University of Tokya, Japan.
Azuma
A
A
Hioki
E
E
Iwasaki
S
S
Kobayashi
Y
Y
Hashimoto
Y
Y
D002273:Carcinogens / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004988:Ethers, Cyclic / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008235:Lyngbya Toxins / Q000494:pharmacology; D015394:Molecular Structure; D019319:Okadaic Acid; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019284:Thapsigargin; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D002273:Carcinogens; D004988:Ethers, Cyclic; D008235:Lyngbya Toxins; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha; D019319:Okadaic Acid; C022176:teleocidins; D013792:Thalidomide; D019284:Thapsigargin; D013755:Tetradecanoylphorbol Acetate