Disruption of cell - matrix attachment results in a loss of prosurvival signals and culminates in programmed cell death, referred to as anoikis , Apoptosis signal- regulating kinase 1(ASKl)/MKK5 is a ubiquitously expressed enzyme that acti vates c-Jun N-terminal kinase/stress-activated protein kinase JNK/SAPK and p38 pathways by direct site specific Ser/Thr phosphoryl ation of their respective MKKs-MKK4/MKK7 for JNK and MKK3/MKK6 for p38 kinases, The kinase activity of ASKl is stimulated by a variety of death signals, including TNF, Fas ligation, reactive oxygen species, and antineoplastic agents , The aim of this study was to investigate the relative importance of ASKl in anOlkls 1n the present study cells which lost their adhesion showed higher rate of cell death in compared to cells which maintained anchorage. 1nterestingly the res ult showed that suspended cells expressing ASK1 were more susceptible to anoikis than suspended cells having no ASK1 1n addition, cellu lar attachment seems to have significant effect on ASKl activity and p38 MAPK protein rather than serum stimulation

Apoptos is s ignal- regulating kinase 1 (ASKl) is a rnitogen-activated protein kinase kinase kinase(MAP3K) 떼 th proapoptotic functlOn 1'he kinase activity of ASKl is stimulated by a variety of death signals , including 1'NFα • Fas ligation, reactive oxygen species, and antineoplastic agents, ASKl promotes cell death by activating the c- Jun N-termina l kinase/stress-activated protein kinase MKK4/MKK7-JNK/SAPK pathway and MKK3/ 1\αCK6-p38 pathway‘ ASKl activity is highly controlled in cells by multiple mechanisms, including phosphorylation, oligome ri zation, and protein- protein ll1 teractlOns Epigallocatechin-3-galla te(EGCG) is the major bioactive polyphenol present in green tea, It possesses anti-oxida nt , a nti - mutagenic‘ a n ti - prote이 ytic ， and anti-proliferative activity, In addition. it has been shown to inhibit cyclin activity, and inhibit cell cycle progression 1n the present study, we exarnined the effect of EGCG on ASKl- overexpressed cells , We expected that EGCG contributes to cell a poptos is by activating ASKl functlOn However, EGCG showed no suppressive effect on cell s urvival of ASKl-overexpressed cells and seemed to promote cell survlval Importantly, the EGCG treatment in creased Akt activity when cells expressed enough amount of ASKl protein, These results s uggest that the presence of ASKl may modify the inhibitory effect of EGCG on cell survival through Akt pathway,