[Apoptosis in P388 leukemia cells induced by specific inhibitors of 5- and 12-lipoxygenase and the product of cyclooxygenase, prostaglandin E2].
We studied the effect of specific inhibitors of 5- and 12-lipoxygenases as well as the product of cyclooxygenase activity, prostaglandin E2, on proliferation and death of P388 leukemia cells. Inhibition of 5- and 12-lipoxygenases in the cells inhibits proliferation and induces apoptosis. The concentrations of baicalein, an inhibitor of 12-lipoxygenase, and AA861, an inhibitor of 5-lipoxygenase, causing a 50% death rate (LC50) proved to be the same, 50 microM. Excessive prostaglandin also inhibited proliferation of the cells and induced apoptosis. The LC50 for prostaglandin E2 was 4 microM. The obtained data suggest that apoptosis in P388 cells after lipoxygenase inhibition can be induced by both deficiency of lipoxygenase products and excess of prostaglandins in the cell.
Grichenko
O E
OE
Shaposhnikova
V V
VV
Kudriavtsev
A A
AA
Korystov
Iu N
IuN
D000818:Animals; D017209:Apoptosis; D016227:Benzoquinones / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D044950:Flavanones / Q000494:pharmacology; D006801:Humans; D007941:Leukemia P388; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D044950:Flavanones; D016859:Lipoxygenase Inhibitors; D011448:Prostaglandin Antagonists; C006680:baicalein; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone