2 MECHANISMS FOR PLATELET-MEDIATED KILLING OF TUMOR-CELLS - ONE CYCLOOXYGENASE DEPENDENT AND THE OTHER NITRIC-OXIDE DEPENDENT

We have tried to identify the cytotoxic effecters in platelet-mediated tumour cell killing, using two tumour cell lines K562 (a chronic myel ogenic leukaemic cell line) and LU99A (a lung cancer cell line), which are both sensitive to platelet cytotoxicity. Cyclo-oxygenase inhibito rs, acetylsalicylic acid (ASA) and indomethacin, effectively inhibited the platelet-mediated killing of K562 cells, but not that of LU99A ce lls. In contrast, inhibitors of the nitric oxide (NO) pathway, N-G-nit ro-L-arginine (L-NA), haemoglobin and methylene blue, reduced the cyto toxic activity of platelets against LU99A, but not against K562. Synth etic analogues of platelet-cyclo-oxygenase products thromboxane A(2)/p rostaglandin H-2 (TXA(2)/PGH(2)) exerted cytotoxicity against K562 cel ls but not against LU99A cells. Electron microscopic study showed that TXA(2)/PGH(2) analogues induced bleb formation and disruption of the plasma membrane of K562 cells. K562 cells enhanced the production of T XA(2) by platelets, as inferred from the accumulation of thromboxane B -2 (TXB(2)), a spontaneous hydrolysis product of TXA(2). LU99A cells h ad no such effects. These results indicate that platelets kill these t wo tumour cell lines through different mechanisms. In K562, the cyclo- oxygenase products TXA(2)/PGH(2). possibly play a significant role, bu t in LU99A the NO pathway seems to be involved.