Y. Nakanishi et al., Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and differentiation of human leukaemia cell lines, EUR J CANC, 37(12), 2001, pp. 1570-1578
Prostaglandins (PG) are known to play important roles in the proliferation
and differentiation of leukaemia cells. The effect of the inhibitors of cyc
looxygenase-2 (COX-2), a rate-limiting enzyme for the synthesis of PG, on t
he proliferation and differentiation of leukaemia cell lines was investigat
ed. COX-2 inhibitors, NS-398 and nabumetone, suppressed the proliferation o
f U-937 and ML-1 cells by inducing a G0/G1 cell-cycle arrest. Cell-cycle ar
rest induced by these COX-2 inhibitors was not associated with an upregulat
ion of the cyclin-dependent kinase inhibitors. COX-2 inhibitors also inhibi
ted the differentiation of these cells induced by interferon-gamma (IFN-gam
ma), tumour necrosis factor-alpha (TNF-alpha) and retinoic acid (RA). Treat
ment with NS-398 did not suppress the levels of PGs produced by these cells
. Although COX-2 antisense oligonucleotide showed a similar inhibitory effe
ct on these cells, its inhibitory effect was smaller than that of NS-398, T
hese results suggest that COX-2 inhibitors may suppress the proliferation a
nd differentiation of leukaemia cells both via COX-2-dependent and -indepen
dent pathways. (C) 2001 Elsevier Science Ltd. All rights reserved.