Effect of seven tricyclic diterpenoids from needles of Taxus media var. Hicksii on stimulus-induced superoxide generation, tyrosyl or serine/threonine phosphorylation and translocation of cytosolic compounds to the cell membrane in human neutrophils.
Taxol has been widely used as an anticancer drug for ovarian, breast, lung and prostate cancer. Some kinds of Taxus plants are widely distributed in the Northeast Asia region. We have isolated seven tricyclic diterpenoids, taxinine, taxagifine, 5-O-cinnamoyltaxacin I triacetate, 5-decinnamoyltaxinine J, 5-cinnamoyl-9-acetyltaxicin I, taxacin and taxol from the needles of Taxus media var. Hicksii, and investigated their effects on stimulus-induced superoxide generation and translocation of cytosolic compounds to the cell membrane in human neutrophils. Six tricyclic diterpenoids used in this experiment suppressed the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and arachidonic acid (AA) in a concentration-dependent manner. Taxinine significantly suppressed the superoxide generation induced by phorbol 12-myristate 13-acetate (PMA). The compounds also suppressed fMLP- and AA-induced tyrosyl or PMA-induced serine/threonine phosphorylation, and translocation of cytosolic compounds, p47 (phox), p67 (phox) and Rac to the cell membrane in parallel with the suppression of the stimulus-induced superoxide generation.
Tong
Jia
J
Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Nankoku Shi, Kochi, Japan.
Lu
Jincai
J
Zhang
Na
N
Chi
Haidong
H
Yamashita
Koichi
K
Manabe
Masanobu
M
Kodama
Hiroyuki
H
D000596:Amino Acids / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D013481:Superoxides / Q000378:metabolism*; D043823:Taxoids / Q000302:isolation & purification / Q000494:pharmacology; D020946:Taxus / Q000737:chemistry*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D000596:Amino Acids; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D016877:Oxidants; D010750:Phosphoproteins; D010936:Plant Extracts; D043823:Taxoids; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020744:rac GTP-Binding Proteins