K. Uefuji et al., Induction of apoptosis by JTE-522, a specific cyclooxygenase-2 inhibitor, in human gastric cancer cell lines, ANTICANC R, 20(6B), 2000, pp. 4279-4284
An increased expression of cyclooxygenase (COX)-2 has been observed in vari
ous cancels including gastric cancer: Although specific COX-2 inhibitors ha
ve a chemopreventive effect on colon cancer; their molecular mechanisms rem
ain unclear To clarify these mechanisms, we investigated the effects of JTE
-522, a newly developed COX-2-specific inhibitor, on gastric cancer cell li
nes (MKN28 and MKN45). The baseline levels of COX-2 expression were higher,
in MKN45 than in MKN28. JTE-522 obviously suppressed the levels of COX-2 m
RNA, COX-2 protein and PGE(2) at a dose of 250 muM in both cancer cells. Ap
optosis was induced at 24 hows after a treatment with JTE-522 (250 muM) in
both cancer cells. To determine the mechanisms of apoptosis induction by JT
E-522, the rime course of the cell cycle and the apoptosis-related protein
levels were examined An increase in the G1 phase and a decrease in the S ph
ase were observed prior to apoptosis. Moreover an increase of c-myc protein
and a decrease of bcl-2 protein were observed in both cells treated with J
TE-522. These findings suggested that JTE-522 could induce apoptosis by blo
cking the cell cycle, enhancing c-myc expression and diminishing bcl-2 expr
ession. JTE-522 also suppressed proliferation activity in both cell lines.
These effects of JTE-522 were more dramatic in MKN45 than in MKN28. Since J
TE-522 strongly suppresses cell growth by inducing apoptosis in gastric can
cel cell lines, it may therefore serve as a chemopreventive agent.