A new potential anti-cancer beta-carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: A proteomic investigation

Annelise Carvalho, Johan Viaene, Guy Vandenbussche, Kris De Braekeleer, Bernard Masereel, Johan Wouters, Florence Souard, Yvan Vander Heyden, Pierre Van Antwerpen, Cédric Delporte, Véronique Mathieu

Research output: Contribution to journalArticlepeer-review

Abstract

Gliomas remain highly fatal due to their high resistance to current therapies. Deregulation of protein synthesis contributes to cancer onset and progression and is a source of rising interest for new drugs. CM16, a harmine derivative with predicted high blood–brain barrier penetration, exerts antiproliferative effects partly through translation inhibition. We evaluated herein how CM16 alters the proteome of glioma cells. The analysis of the gel-free LC/MS and auto-MS/MS data showed that CM16 induces time- and concentration-dependent significant changes in the total ion current chromatograms. In addition, we observed spontaneous clustering of the samples according to their treatment condition and their proper classification by unsupervised and supervised analyses, respectively. A two-dimensional gel-based approach analysis allowed us to identify that treatment with CM16 may downregulate four key proteins involved in glioma aggressiveness and associated with poor patient survival (HspB1, BTF3, PGAM1, and cofilin), while it may upregulate galectin-1 and Ebp1. Consistently with the protein synthesis inhibition properties of CM16, HspB1, Ebp1, and BTF3 exert known roles in protein synthesis. In conclusion, the downregulation of HspB1, BTF3, PGAM1 and cofilin bring new insights in CM16 antiproliferative effects, further supporting CM16 as an interesting protein synthesis inhibitor to combat glioma.

Original languageEnglish
Pages (from-to)32-42
Number of pages11
JournalDrug Development Research
Volume81
Issue number1
DOIs
Publication statusPublished - Feb 2020

Keywords

  • beta-carboline
  • BTF3
  • cancer
  • glioma
  • HspB1
  • PGAM1
  • protein synthesis

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