ArticleJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry2023
Targeting cancer lactate metabolism with synergistic combinations of synthetic catalysts and monocarboxylate transporter inhibitors.
Article in Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- Multichiral Half-Sandwich Ru(II) and Os(II) Anticancer Complexes Containing a Glutathione Synthesis Inhibitor.Organometallics · 2025Article
- Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies.MedComm · 2025Review
- L- and D-Lactate: unveiling their hidden functions in disease and health.Cell communication and signaling : CCS · 2025Review
- Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells.Bioscience reports · 2024Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Synthetic anticancer catalysts offer potential for low-dose therapy and the targeting of biochemical pathways in novel ways. Chiral organo-osmium complexes, for example, can catalyse the asymmetric transfer hydrogenation of pyruvate, a key substrate for energy generation, in cells. However, small-molecule synthetic catalysts are readily poisoned and there is a need to optimise their activity before this occurs, or to avoid this occurring. We show that the activity of the synthetic organometallic redox catalyst [Os(p-cymene)(TsDPEN)] (1), which can reduce pyruvate to un-natural D-lactate in MCF7 breast cancer cells using formate as a hydride source, is significantly increased in combination with the monocarboxylate transporter (MCT) inhibitor AZD3965. AZD3965, a drug currently in clinical trials, also significantly lowers the intracellular level of glutathione and increases mitochondrial metabolism. These synergistic mechanisms of reductive stress induced by 1, blockade of lactate efflux, and oxidative stress induced by AZD3965 provide a strategy for low-dose combination therapy with novel mechanisms of action.
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Registered trials
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