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



Butterworth, Michael, Pettitt, Andrew, Varadarajan, Shankar ORCID: 0000-0002-8827-6567 and Cohen, Gerald M
(2016) BH3 profiling and a toolkit of BH3-mimetic drugs predict anti-apoptotic dependence of cancer cells. BRITISH JOURNAL OF CANCER, 114 (6). pp. 638-641.

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>We use BH3 profiling in combination with cell death analyses using a chemical inhibitor toolkit to assess chemosensitivity of cancer cells.<h4>Results</h4>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.<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: BH3 profiling, A-1331852, A-1210477, ABT-199, MCL-1, BCL-XL
Depositing User: Symplectic Admin
Date Deposited: 21 Apr 2016 13:44
Last Modified: 15 Dec 2022 16:31
DOI: 10.1038/bjc.2016.49
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3000181