The NF-κB inhibitor DHMEQ decreases survival factors, overcomes the protective activity of microenvironment and synergizes with chemotherapy agents in classical Hodgkin lymphoma

Marta Celegato, Cinzia Borghese, Kazuo Umezawa, Naike Casagrande, Alfonso Colombatti, Antonino Carbone, Donatella Aldinucci

Research output: Contribution to journalArticlepeer-review

Abstract

The NF-κB inhibitor DHMEQ has shown preclinical activity in classical Hodgkin Lymphoma (cHL).Here we evaluated if DHMEQ could affect microenvironmental interactions and formation and improve the activity of drugs used in relapsed/refractory cHL. We demonstrated that DHMEQ down-regulated the NF-κB target genes IRF4 and CD40, the secretion of IL-6, CCL5, CCL17 and generated ROS. Cytotoxicity, CD30 down-modulation and CD30 shedding by DHMEQ were prevented by ROS scavenger NAC. DHMEQ overcame stimuli from CD40 engagement and fibroblasts and enhanced doxorubicin, cisplatin and gemcitabine activity. Our results suggest that DHMEQ may be a promising agent for future therapeutic strategies in cHL.

Original languageEnglish
Pages (from-to)26-34
Number of pages9
JournalCancer Letters
Volume349
Issue number1
DOIs
Publication statusPublished - Jul 10 2014

Keywords

  • CD30
  • Hodgkin lymphoma
  • NF-κB inhibitors
  • Reactive oxygen species
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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