ArticleProceedings of the National Academy of Sciences of the United States of America2015
Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 78 citations in OpenAlex.
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- Recent Advances in Anticancer Research of Osmium and Rhodium Complexes.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Cancer 3D Models for Metallodrug Preclinical Testing.International journal of molecular sciences · 2023Review
- Mitochondria as a target of third row transition metal-based anticancer complexes.Current opinion in chemical biology · 2023Review
- Genome-wide CRISPR Screen Reveal Targets of Chiral Gold(I) Anticancer Compound in Mammalian Cells.ACS omega · 2022Article
- Self-assembled ruthenium and osmium nanosystems display a potent anticancer profile by interfering with metabolic activity.Inorganic chemistry frontiers · 2022Article
- NMR studies of group 8 metallodrugs:Dalton transactions (Cambridge, England : 2003) · 2021Article
- Heterogeneity of Response to Iron-Based Metallodrugs in Glioblastoma Is Associated with Differences in Chemical Structures and Driven by FAS Expression Dynamics and Transcriptomic Subtypes.International journal of molecular sciences · 2021Article
- Anticancer gold(iii)-bisphosphine complex alters the mitochondrial electron transport chain to induceChemical science · 2021Article
- Osmium-arene complexes with high potency towards Mycobacterium tuberculosis.Metallomics : integrated biometal science · 2021Article
- Dose- and time-dependent tolerability and efficacy of organo-osmium complex FY26 and its tissue pharmacokinetics in hepatocarcinoma-bearing mice.Metallomics : integrated biometal science · 2021Article
- Metallodrugs are unique: opportunities and challenges of discovery and development.Chemical science · 2020Review
- Cancer cell-selective modulation of mitochondrial respiration and metabolism by potent organogold(iii) dithiocarbamates.Chemical science · 2020Article
- In Vivo Selectivity and Localization of Reactive Oxygen Species (ROS) Induction by Osmium Anticancer Complexes That Circumvent Platinum Resistance.Journal of medicinal chemistry · 2018Article
- Small Molecule Catalysts with Therapeutic Potential.Molecules (Basel, Switzerland) · 2018Review
- Halide Control ofOrganometallics · 2017Article
- Synchrotron X-Ray Fluorescence Nanoprobe Reveals Target Sites for Organo-Osmium Complex in Human Ovarian Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- In-Cell Activation of Organo-Osmium(II) Anticancer Complexes.Angewandte Chemie (International ed. in English) · 2017Article
- Antagonizing STAT5B dimerization with an osmium complex.Scientific reports · 2016Article
- Nucleotide Binding Preference of the Monofunctional Platinum Anticancer-Agent Phenanthriplatin.Chemistry (Weinheim an der Bergstrasse, Germany) · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
The organometallic "half-sandwich" compound [Os(η(6)-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up-regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.