Journal article
BH3 mimetic drugs cooperate with Temozolomide, JQ1 and inducers of ferroptosis in killing glioblastoma multiforme cells
D Moujalled, AG Southon, E Saleh, K Brinkmann, F Ke, M Iliopoulos, RS Cross, MR Jenkins, D Nhu, Z Wang, MX Shi, RM Kluck, G Lessene, S Grabow, AI Bush, A Strasser
Cell Death and Differentiation | Published : 2022
Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer, with treatment options often constrained due to inherent resistance of malignant cells to conventional therapy. We investigated the impact of triggering programmed cell death (PCD) by using BH3 mimetic drugs in human GBM cell lines. We demonstrate that co-targeting the pro-survival proteins BCL-XL and MCL-1 was more potent at killing six GBM cell lines compared to conventional therapy with Temozolomide or the bromodomain inhibitor JQ1 in vitro. Enhanced cell killing was observed in U251 and SNB-19 cells in response to dual treatment with TMZ or JQ1 combined with a BCL-XL inhibitor, compared to single agent ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by a Programme Grant (GNT1113133) to AS and GL, Research Fellowships (GNT1116937 to AS and GNT1117089 to GL) from the Australian NHMRC, the Leukemia & Lymphoma Society of America (Specialized Centre of Research [SCOR] grant no. 7015-18 to AS and GL), a grant-in-aid from the Cure Cancer Foundation (Australia), Leukaemia Foundation Australia grant (SG), the Lady Tata Memorial Trust (SG) and a grant from Cure Brain Cancer Australia grant (AS). Work in the laboratories of the authors was made possible through Victorian State Government Operational Infrastructure Support (OIS) and Australian Government NHMRC Independent Research Institute Infrastructure Support (IRIIS) Scheme.