Cancer Letters
Volume 318, Issue 1 , Pages 53-60, 1 May 2012

Bcl-XL, but not Bcl-2, can protect human B-lymphoma cell lines from parthenolide-induced apoptosis

  • Alan T. Yeo

      Affiliations

    • Department of Biology, Boston University, Boston, MA 02215, USA
    • ,
  • John A. Porco Jr.

      Affiliations

    • Department of Chemistry, Boston University, Boston, MA 02215, USA
    • Center for Chemical Methodology and Library Development, Boston University, Boston, MA 02215, USA
    • ,
  • Thomas D. Gilmore

      Affiliations

    • Department of Biology, Boston University, Boston, MA 02215, USA
    • Center for Chemical Methodology and Library Development, Boston University, Boston, MA 02215, USA
    • Corresponding Author InformationCorresponding author at: Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA. Tel.: +1 617 353 5444; fax: +1 617 353 6340.

Received 3 July 2011; received in revised form 29 November 2011; accepted 30 November 2011. published online 26 December 2011.

Abstract 

In this report, we investigated the effects of the natural product parthenolide on human B-lymphoma cell lines. We show that parthenolide inhibited NF-κB transcription factor c-Rel (REL). In addition, the sensitivity of several human B-lymphoma cell lines to parthenolide-induced apoptosis inversely correlated with their levels of anti-apoptosis protein Bcl-XL. Furthermore, ectopic expression of Bcl-XL (but not Bcl-2) in two B-lymphoma cell lines decreased their sensitivity to parthenolide-induced apoptosis. Finally, over-expression of a transforming mutant of REL, which increased expression of endogenous Bcl-XL, decreased the sensitivity of BJAB B-lymphoma cells to parthenolide-induced apoptosis. These results demonstrate that the NF-κB target gene products Bcl-XL and Bcl-2 can play different roles in protecting B-lymphoma cells from chemical-induced apoptosis.

Abbreviations: ABC, activated B cell, DLBCL, diffuse large B-cell lymphoma, DMEM, Dulbecco’s modified Eagle’s medium, EF10, DMEM supplemented with 10% FBS, EF20, DMEM supplemented with 20% FBS, FBS, fetal bovine serum, GCB, germinal center B-cell, IKK, IκB kinase, PARP, poly(ADP-ribose) polymerase, PEI, polyethylenimine, PMSF, phenylmethanesulfonyl fluoride, ROS, reactive oxygen species

Keywords: Parthenolide, NF-κB, Bcl-XL, Bcl-2, B-cell lymphoma, Apoptosis

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PII: S0304-3835(11)00736-1

doi:10.1016/j.canlet.2011.11.035

Cancer Letters
Volume 318, Issue 1 , Pages 53-60, 1 May 2012

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