Poster Presentation 26th Lorne Cancer Conference 2014

Evaluation of a novel epigenetic therapy for the treatment of colon cancer (#268)

Lars Togel , Rebecca Nightingale 1 , Anderly C Chueh 1 , Hoanh Tran 1 , Timothy C Gahman 2 , Andrew K Shiau 2 , John M Mariadason 1
  1. Oncogenic Transcription Laboratory, Ludwig Cancer Research, Melbourne, Victoria, Australia
  2. Small Molecule Development Laboratory, Ludwig Cancer Research, San Diego, California, USA

Oncogenic cMYC is overexpressed in 90% of all colon cancers, and its expression is associated with poor prognosis. Recently, a novel class of small molecule inhibitors of the bromodomain and extra-terminal (BET) protein family have demonstrated robust inhibition of cMYC expression and tumour cell growth in haematological and some solid cancer cell lines. The aim of this work was to test the efficacy of bromodomain inhibitors to induce growth arrest in colon cancer cells by mediating the transcriptional repression of cMYC. Using MTS assay, we profiled the sensitivity of 20 colon cancer cell lines to the bromodomain-inhibitor JQ1 and identified a subset of sensitive lines which arrest in G1 phase of the cell cycle upon treatment. Monitoring of JQ1-induced changes in cMYC expression levels by western blot and qPCR revealed a positive correlation between levels in cMYC reduction and growth inhibition (r=0.5329, p=0.0188). Knock-down of cMYC diminished JQ1 efficacy to suppress growth of sensitive cell lines and, likewise, cMYC overexpression rescued sensitive cell lines from the growth inhibitory effect of JQ1 effects. Our data demonstrates that JQ1-treatment represses cMYC expression in colon cancer cells, and establishes a clear correlation with JQ1-induced growth inhibition.