AIM:To investigate the role of the mitochondrial pathway inJTE-522-induced apoptosis and to investigate therelationship between cytochrome C re!case,caspase activityand loss,of mitochondrial membrane potential(ΔΨm).METHODS:Cell culture,cell counting,ELISA assay,TUNEL,flow cymetry,Western blot and fluorometric assaywere employed to investigate the effect of JTE-522 on cellproliferation and apoptosis in AGS cells and relatedmolecular mechanism.RESULTS:JTE-522 inhibited the growth of AGS cells andinduced the apoptosis.Caspases 8 and 9 were activatedduring apoptosis as judged by the appearance of clcavageproducts from procaspase and the caspase activities tocleave specific fluorogenic substrates.To elucidate whetherthe activation of caspases 8 and 9 was required for theapoptosis induction,we examined the effect of caspase-specific inhibitors on apoptosis.The results showed thatcaspase inhibitors significantly inhibited the apoptosisinduced by JTE-522.In addition,the membranetranslocation of Bax and cytosolic release of cytochrome Caccompanying with the decrease of the uptake of Rhodamin123,were detected at an early stage of apoptosis.Furthermore,Bax translocation,cytochrome C release,andcaspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO.CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of △ψm and JTE-522-induced apoptosis in AGS cells. AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate therelationship between cytochrome C re! Case, caspase activity and loss, of mitochondrial membrane potential (ΔΨm) .METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cymetry, Western blot and fluorometric assaywere employed to investigate the effect of JTE-522 on cellproliferation and apoptosis in AGS cells and related molecular mechanisms.RESULTS: JTE-522 inhibited the growth of AGS cells andinduced the apoptosis. Caspases 8 and 9 were activatedduring apoptosis as judged by the appearance of clcavageproducts from procaspase and the caspase activities tocleave specific fluorogenic substrates.To elucidate whetherthe activation of caspases 8 and 9 was required for theapoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. Addition, the membrane transfer location of Bax and cytosolic release of cytochrome Caccompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Fultrthermore, Bax translocation, cytochrome C release, and caspase 9 activation by blocked by Z-VAD.fmk and Z-IETD -CHO.CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of △ ψm and JTE-522-induced apoptosis in AGS cells.