Abstract
Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mito- chondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its thera- peutic potential following systemic delivery. This provides evidence that AuDTC is an effective modulator of mitochondrial respiration worthy of clinical development in the context of TNBC. One sentence summary: Metabolic-targeting of triple-negative breast cancer by gold anticancer agent may provide efficacious therapy.
Document Type
Article
Publication Date
12-2023
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.biopha.2023.116010
Funding Information
National Institutes of Health-NCI grant R01CA258421-01 (S.G.A.), and Oberlin College (G.F.K.). The authors also acknowledge support of the Center for Pharmaceutical Research and Innovation (CPRI, NIH P20 GM130456).
Repository Citation
Mertens, R. Tyler; Kim, Jong Hyun; Ofori, Samuel; Olelewe, Chibuzor Ngozi; Kamitsuka, Paul J.; Kwakye, Gunnar F.; and Awuah, Samuel G., "A gold-based inhibitor of oxidative phosphorylation is effective against triple negative breast cancer" (2023). Markey Cancer Center Faculty Publications. 200.
https://uknowledge.uky.edu/markey_facpub/200
Notes/Citation Information
© 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).