Combined effects of histone deacetylase inhibitor and rituximab on non-Hodgkin's B-lymphoma cells apoptosis

Wei Li Zhao, Lan Wang, Yuan Hua Liu, Jin Song Yan, Christophe Leboeuf, Yan Yan Liu, Wei Li Wu, Anne Janin, Zhu Chen, Sai Juan Chen

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Objective: The anti-CD20 monoclonal antibody rituximab has shown promising results in the clinical treatment of patients with B-cell non-Hodgkin's lymphoma (B-NHL). However, its therapeutic effect could still be improved. Methods: This study examined the anti-tumor activity of rituximab combined with histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in CD20-positive B-NHL cell lines, as well as in primary B-NHL cells and a murine B-NHL model. Results: The combination treatment sensitized B-NHL cells to apoptosis in a synergistic manner, concomitant with mitochondrial instability and Bcl-2/Bcl-XL downregulation. Particularly in Daudi cells relatively resistant to rituximab, these events were associated with nuclear factor-κB (NF-κB) inactivation and c-Myc degradation. SAHA presented functional complementation with rituximab, through decreasing IKKα/β and IκBα phosphorylation, thus preventing NF-κB nuclear translocation. In addition, SAHA induced IκBα cleavage to a stable inhibitory form and caused NF-κB degradation in response to caspase-3 activation. More importantly, rituximab-SAHA combination significantly promoted primary B-NHL cells apoptosis and improved survival time of a severe combined immunodeficient mouse lymphoma model established with intravenous injection of Daudi cells. Conclusion: These findings emphasized the value of targeting apoptosis signaling pathway in lymphoma therapy. Rituximab in conjunction with histone deacetylase inhibitor may represent a novel strategy in treating patients with B-NHL.

Original languageEnglish (US)
Pages (from-to)1801-1811
Number of pages11
JournalExperimental Hematology
Volume35
Issue number12
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Combined effects of histone deacetylase inhibitor and rituximab on non-Hodgkin's B-lymphoma cells apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Zhao, W. L., Wang, L., Liu, Y. H., Yan, J. S., Leboeuf, C., Liu, Y. Y., Wu, W. L., Janin, A., Chen, Z., & Chen, S. J. (2007). Combined effects of histone deacetylase inhibitor and rituximab on non-Hodgkin's B-lymphoma cells apoptosis. Experimental Hematology, 35(12), 1801-1811. https://doi.org/10.1016/j.exphem.2007.06.009