Two mechanisms for platelet-mediated killing of tumour cells: one cyclo-oxygenase dependent and the other nitric oxide dependent.
We have tried to identify the cytotoxic effectors in platelet-mediated tumour cell killing, using two tumour cell lines K562 (a chronic myelogenic leukaemic cell line) and LU99A (a lung cancer cell line), which are both sensitive to platelet cytotoxicity. Cyclo-oxygenase inhibitors, acetylsalicylic acid (ASA) and indomethacin, effectively inhibited the platelet-mediated killing of K562 cells, but not that of LU99A cells. In contrast, inhibitors of the nitric oxide (NO) pathway. NG-nitro-1-arginine (L-NA), haemoglobin and methylene blue, reduced the cytotoxic activity of platelets against LU99A, but not against K562. Synthetic analogues of platelet cyclo-oxygenase products thromboxane A2/ prostaglandin H2(TXA2/PGH2) exerted cytotoxicity against K562 cells but not against LU99A cells. Electron microscopic study showed that TXA2/PGH2 analogues induced bleb formation and disruption of the plasma membrane of K562 cells. K562 cells enhanced the production of TXA2 by platelets, as inferred from the accumulation of thromboxane B2 (TXB2), a spontaneous hydrolysis product of TXA2. LU99A cells had no such effects. These results indicate that platelets kill these two tumour cell lines through different mechanisms. In K562, the cyclooxygenase products TXA2/PGH2 possibly play a significant role but in LU99A the NO pathway seems to be involved.
Department of Clinical Laboratory Technology, Ehime College of Health Science, Japan.
M
M
Okada
T
T
Sagawa
A
A
Tominaga
T
T
Kodama
Y
Y
Hitsumoto
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006454:Hemoglobins / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013928:Thromboxane A2; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D006454:Hemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D013929:Thromboxane B2; D013928:Thromboxane A2; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D001241:Aspirin; D008751:Methylene Blue; D007213:Indomethacin