Journal article

Phenotypic screen for oxygen consumption rate identifies an anti-cancer naphthoquinone that induces mitochondrial oxidative stress

Frances L Byrne, Ellen M Olzomer, Gabriella R Marriott, Lake-Ee Quek, Alice Katen, Jacky Su, Marin E Nelson, Gene Hart-Smith, Mark Larance, Veronica F Sebesfi, Jeff Cuff, Gabriella E Martyn, Elizabeth Childress, Stephanie J Alexopoulos, Ivan K Poon, Maree C Faux, Antony W Burgess, Glen Reid, Joshua A McCarroll, Webster L Santos Show all

Redox Biology | ELSEVIER | Published : 2020

Abstract

A hallmark of cancer cells is their ability to reprogram nutrient metabolism. Thus, disruption to this phenotype is a potential avenue for anti-cancer therapy. Herein we used a phenotypic chemical library screening approach to identify molecules that disrupted nutrient metabolism (by increasing cellular oxygen consumption rate) and were toxic to cancer cells. From this screen we discovered a 1,4-Naphthoquinone (referred to as BH10) that is toxic to a broad range of cancer cell types. BH10 has improved cancer-selective toxicity compared to doxorubicin, 17-AAG, vitamin K3, and other known anti-cancer quinones. BH10 increases glucose oxidation via both mitochondrial and pentose phosphate pathwa..

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Grants

Awarded by Hope Funds for Cancer Research


Awarded by Cancer Institute NSW ECF


Funding Acknowledgements

FLB was supported by a postdoctoral fellowship from the Hope Funds for Cancer Research (HFCR-14-06-04) and is currently supported by a Cancer Institute NSW ECF (2018/ECF003). Financial support was provided in part by a UNSW faculty collaboration grant to KLH and NK. JM is supported by a Cancer Institute NSW CDF. GEM was supported by an Australian Postgraduate Award. KGRQ is supported by a UNSW Sydney Scientia Fellowship.