BH3 profiling and a toolkit of BH3-mimetic drugs predict anti-apoptotic dependence of cancer cells

  • Br J Cancer. 2016 Mar 15;114(6):638-41. doi: 10.1038/bjc.2016.49.
Michael Butterworth  1  2 ,  Andrew Pettitt  1 ,  Shankar Varadarajan  1  2 ,  Gerald M Cohen  1  2
Affiliations
  • 1. Departments of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GE, UK.
  • 2. Department of Pharmacology, University of Liverpool, Liverpool L69 3GE, UK.
PMID: 26954718 DOI: 10.1038/bjc.2016.49
Abstract

Background: Anti-apoptotic Bcl-2 Family members antagonise Apoptosis by sequestering their pro-apoptotic counterparts. The balance between the different Bcl-2 Family members forms the basis of BH3 profiling, a peptide-based technique used to predict chemosensitivity of Cancer cells. Recent identification of cell-permeable, selective inhibitors of Bcl-2, Bcl-xL and Mcl-1, further facilitates the determination of the Bcl-2 Family dependency of Cancer cells.

Methods: We use BH3 profiling in combination with cell death analyses using a chemical inhibitor toolkit to assess chemosensitivity of Cancer cells.

Results: Both BH3 profiling and the inhibitor toolkit effectively predict chemosensitivity of cells addicted to a single anti-apoptotic protein but a combination of both techniques is more instructive when cell survival depends on more than one anti-apoptotic protein.

Conclusions: The inhibitor toolkit provides a rapid, inexpensive and simple means to assess the chemosensitivity of tumour cells and in conjunction with BH3 profiling offers much potential in personalising Cancer therapy.

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