Premium
NF‐κB‐dependency and consequent regulation of IL‐8 in echinomycin‐induced apoptosis of HT‐29 colon cancer cells
Author(s) -
Park Ju Youn,
Chang JaeHo,
Bae Keum Seok,
Lee Kyoung Ho,
Choi Sun Ju,
Park Joo Young,
Ryang Yong Suk,
Kim SooKi
Publication year - 2008
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2008.07.003
Subject(s) - apoptosis , nf κb , chemistry , caspase 9 , caspase 3 , caspase , chemokine , microbiology and biotechnology , biology , cancer research , receptor , biochemistry , programmed cell death
The present study was to see whether echinomycin‐induced apoptosis would be NF‐κB‐dependent and if so, whether echinomycin would activate or inhibit NF‐κB as well as resultant chemokine IL‐8 expression. In HT‐29 cells echinomycin activated NF‐κB in time‐dependent manner. EMSA in the presence of antibodies specific for p50 and p65 subunits indicated that echinomycin‐induces the translocation of p50–p65 heterodimeric subunits of NF‐κB. Levels of IκB were detected at initial echinomycin treatment and thereafter decreased, faintly seen after a 6 h treatment. In contrast p‐IκB levels were clearly detected throughout 6–24 h of echinomycin treatment, albeit initially fainted. To clarify the role of NF‐κB on IL‐8 expression in echinomycin‐mediated apoptosis of HT‐29 cells, ELISA plus RT‐PCR clearly showed that IL‐8 production is inducible by echinomycin treatment. Using a specific inhibitor, IL‐8 regulation at echinomycin treatment in HT‐29 cells occurred via both caspase‐3 and NF‐κB‐dependent signal pathway. To confirm whether two different pathways (NF‐κB and caspase) would be coupled, only NF‐κB inhibitor (PDTC) and caspase‐3 specific inhibitor (Z‐DEVD‐FMK) together significantly attenuated echinomycin‐initiated apoptosis of HT‐29 cells, pretreatment of HT‐29 cells with PDTC rarely affected echinomycin‐induced caspase‐3 activation. So echinomycin‐induced apoptosis in HT‐29 cells occurs via NF‐κB activation independent of caspase‐3 activation modulating the resultant‐linked key chemokine IL‐8 expression and echinomycin‐induced apoptosis is NF‐κB‐dependant and directly related to NF‐κB activation, consequently regulating IL‐8 expression.