Journal article
The epigenetic regulator I-BET151 induces BIM-dependent apoptosis and cell cycle arrest of human melanoma cells
SJ Gallagher, B Mijatov, D Gunatilake, JC Tiffen, K Gowrishankar, L Jin, GM Pupo, C Cullinane, RK Prinjha, N Smithers, GA Mcarthur, H Rizos, P Hersey
Journal of Investigative Dermatology | Published : 2014
DOI: 10.1038/jid.2014.243
Abstract
Epigenetic changes are widespread in melanoma and contribute to the pathogenic biology of this disease. In the present study, we show that I-BET151, which belongs to a new class of drugs that target the BET family of epigenetic "reader" proteins, inhibits melanoma growth in vivo and induced variable degrees of apoptosis in a panel of melanoma cells. Apoptosis was caspase dependent and associated with G1 cell cycle arrest. All melanoma cells tested had increased levels of the BH3 proapoptotic protein BIM, which appeared to be regulated by the BRD2 BET protein and to some extent by BRD3. In contrast, knockdown experiments indicated that inhibition of BRD4 was associated with decreased levels o..
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Funding Acknowledgements
We thank Warren Kaplan (Garvan Institute of Medical Research) for his assistance in microarray analysis and Kerry Ardley for technical assistance in the conduct of the in vivo study. This work was supported by program grant 633004 from the Australian National Health and Medical Research Council (NHMRC) and the Cancer Institute NSW and the Melanoma Foundation of the University of Sydney.