NF-κB-dependency and consequent regulation of IL-8 in echinomycin-induced apoptosis of HT-29 colon cancer cells

Ju Youn Park, Jae Ho Chang, Keumseok Bae, Kyoung Ho Lee, Sun Ju Choi, Joo Young Park, Yong Suk Ryang, Soo-Ki Kim

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Abstract

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.

Original languageEnglish
Pages (from-to)1207-1214
Number of pages8
JournalCell Biology International
Volume32
Issue number10
DOIs
Publication statusPublished - 2008 Oct 1

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Echinomycin
Interleukin-8
Colonic Neoplasms
Apoptosis
HT29 Cells
Caspase 3
Chemokines
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Park, Ju Youn ; Chang, Jae Ho ; Bae, Keumseok ; Lee, Kyoung Ho ; Choi, Sun Ju ; Park, Joo Young ; Ryang, Yong Suk ; Kim, Soo-Ki. / NF-κB-dependency and consequent regulation of IL-8 in echinomycin-induced apoptosis of HT-29 colon cancer cells. In: Cell Biology International. 2008 ; Vol. 32, No. 10. pp. 1207-1214.
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abstract = "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.",
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NF-κB-dependency and consequent regulation of IL-8 in echinomycin-induced apoptosis of HT-29 colon cancer cells. / Park, Ju Youn; Chang, Jae Ho; Bae, Keumseok; Lee, Kyoung Ho; Choi, Sun Ju; Park, Joo Young; Ryang, Yong Suk; Kim, Soo-Ki.

In: Cell Biology International, Vol. 32, No. 10, 01.10.2008, p. 1207-1214.

Research output: Contribution to journalArticle

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