Induction of apoptosis by JTE-522, a specific cyclooxygenase-2 inhibitor, in human gastric cancer cell lines

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.