[Growth inhibition and induction of tumor cell death by phospholipase A2 and lipoxygenase inhibitors].
We studied the effect of arachidonic acid metabolism inhibitors in a wide concentration range on the proliferation and death of lympholeukemia cells P-388. Proliferation of the cells was estimated by metaphase frequency and the proportion of cells in S phase; cellular death was determined by their lysis, trypan blue staining, damaged nuclei, the proportion of cells with subdiploid DNA content, and DNA fragmentation. Low concentrations of phospholipase A2 and lipoxygenase inhibitors were shown to stimulate cell division, while higher concentrations inhibited it by blocking G1-S transition and inducing apoptotic cellular death. Indomethacin, a cyclooxygenase inhibitor, had no effect on proliferation and induced no cell death at concentrations up to 10 microM. Inhibitors of phospholipase A2 and lipoxygenase also inhibited tumor growth in mice.
Shaposhnikova
V V
VV
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, pr. Nauki, Pushchino, Moscow oblast, 142292 Russia.
Kublik
L N
LN
Narimanov
A A
AA
Levitman
M Kh
MKh
Orlova
O E
OE
Kudriavtsev
A A
AA
Leshchenko
V V
VV
Korystov
Iu N
IuN
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007941:Leukemia P388; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D009368:Neoplasm Transplantation; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D014407:Tumor Cells, Cultured
D000098:Acetophenones; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol; D008084:Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide; D007213:Indomethacin