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
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..View full abstract
Awarded by Hope Funds for Cancer Research
Awarded by Cancer Institute NSW ECF
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.