Bid mediates anti-apoptotic COX-2 induction through the IKKβ/NFκB pathway due to 5-MCDE exposure

W. Luo, J. Li, D. Zhang, T. Cai, L. Song, X. M. Yin, D. Desai, S. Amin, J. Chen, C. Huang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Although Bid is considered to be a cell apoptotic mediator, current studies suggest that it has a possible role in cell survival for mouse embryonic fibroblasts (MEFs) in response to low doses of anti-(±)-5- methylchrysene-1,2-diol-3,4-epoxide (≤0.25μM) (5-MCDE). We found that the exposure of MEFs to 0.25 μM 5-MCDE resulted in a slight apoptotic induction, while this apoptotic response was substantially increased in the Bid knockout MEFs (Bid-/-), suggesting that there is a Bid-mediated anti-apoptotic function in this response. This notion was further supported by the findings that re-constitution expression of Bid into Bid-/- cells could inhibit the increased apoptosis. Further studies show that the antiapoptotic function of Bid was associated with its mediation of COX-2 expression. This conclusion was based the reduction of COX-2 expression in Bid-/- cells, the restoration of low sensitivity to 5-MCDE-induced apoptosis by the introduction of Bid into Bid-/- cells, and increased sensitivity of WT MEFs to 5-MCDE-induced apoptosis by the knockdown of COX-2 expression. Furthermore, we found that Bid mediated COX-2 expression through the IKKβ/NFκB pathway because the deficiency of Bid in Bid-/- MEFs resulted in the blockade of IKK/NFκB activation and knockout of IKKβ caused abrogation of COX-2 expression induced by 5-MCDE. Collectively, our results demonstrate that Bid is critical for COX-2 induction through the IKKβ/NFκB pathway, which mediates its anti-apoptotic function, in cell response to low doses of 5-MCDE exposure.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalCurrent Cancer Drug Targets
Volume10
Issue number1
DOIs
StatePublished - Feb 2010

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

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