ArticleScientific reports2016
A novel approach using C. elegans DNA damage-induced apoptosis to characterize the dynamics of uptake transporters for therapeutic drug discoveries.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
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- Potent anticancer activity of a novel iridium metallodrug via oncosis.Cellular and molecular life sciences : CMLS · 2022Article
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- A Pilot Study of All-Computational Drug Design Protocol-From Structure Prediction to Interaction Analysis.Frontiers in chemistry · 2020Article
- Anti-cancer effect of doxorubicin is mediated by downregulation of HMG-Co A reductase via inhibition of EGFR/Src pathway.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Differential Expression of Histone H3.3 Genes and Their Role in Modulating Temperature Stress Response inGenetics · 2018Article
- UNG-1 and APN-1 are the major enzymes to efficiently repair 5-hydroxymethyluracil DNA lesions in C. elegans.Scientific reports · 2018Article
- Imaging the Pharynx to Measure the Uptake of Doxorubicin inBio-protocol · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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Abstract
Organic cation transporter (OCT) function is critical for cellular homeostasis. C. elegans lacking OCT-1 displays a shortened lifespan and increased susceptibility to oxidative stress. We show that these phenotypes can be rescued by downregulating the OCT-1 paralogue, OCT-2. Herein, we delineate a biochemical pathway in C. elegans where uptake of genotoxic chemotherapeutics such as doxorubicin and cisplatin, and subsequent DNA damage-induced apoptosis of germ cells, are dependent exclusively upon OCT-2. We characterized OCT-2 as the main uptake transporter for doxorubicin, as well as a number of other therapeutic agents and chemical compounds, some identified through ligand-protein docking analyses. We provide insights into the conserved features of the structure and function and gene regulation of oct-1 and oct-2 in distinct tissues of C. elegans. Importantly, our innovative approach of exploiting C. elegans uptake transporters in combination with defective DNA repair pathways will have broad applications in medicinal chemistry.
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