ArticleMolecular cancer therapeutics2012
Inhibition of OCTN2-mediated transport of carnitine by etoposide.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma.PloS one · 2020Trial
- Can levocarnitine supplementation improve fatigue caused by sunitinib as a treatment for renal cell carcinoma? A single-center prospective pilot study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2019Trial
- Lipopeptides fromBiotech (Basel (Switzerland)) · 2026Article
- Carnitine deficiency augments methotrexate-mediated acute renal injury in rats.Journal of the Egyptian National Cancer Institute · 2025Article
- Carnitine Shuttle and Ferroptosis in Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Transporters and drug secretion into human breast milk.Expert opinion on drug metabolism & toxicology · 2025Review
- Sirtuin 3 reinforces acylcarnitine metabolism and maintains thermogenesis in brown adipose tissue of aging mice.Aging cell · 2024Article
- Dysfunction of the carnitine cycle in tumor progression.Heliyon · 2024Review
- Metabolic Contrasts: Fatty Acid Oxidation and Ketone Bodies in Healthy Brains vs. Glioblastoma Multiforme.International journal of molecular sciences · 2024Review
- Contribution and expression of renal drug transporters in renal cell carcinoma.Frontiers in pharmacology · 2024Review
- Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Smart Strategies to Overcome Drug Delivery Challenges in the Musculoskeletal System.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy.Pharmaceutics · 2023Review
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
- Article
- Overview of Drug Transporters in Human Placenta.International journal of molecular sciences · 2021Review
- Changes in carnitine levels through induction chemotherapy in head and neck cancer patients as a potential cause of therapy-related malaise.BMC cancer · 2021Article
- The Role of the Carnitine/Organic Cation Transporter Novel 2 in the Clinical Outcome of Patients With Locally Advanced Esophageal Carcinoma Treated With Oxaliplatin.Frontiers in pharmacology · 2021Article
- Cellular Mechanisms Accounting for the Refractoriness of Colorectal Carcinoma to Pharmacological Treatment.Cancers · 2020Review
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
OCTN2 is a bifunctional transporter that reabsorbs filtered carnitine in a sodium-dependent manner and secretes organic cations into urine as a proton antiport mechanism. We hypothesized that inhibition of OCTN2 by anticancer drugs can influence carnitine resorption. OCTN2-mediated transport inhibition by anticancer drugs was assessed using cells transfected with human OCTN2 (hOCTN2) or mouse Octn2 (mOctn2). Excretion of carnitine and acetylcarnitine was measured in urine collected from mice and pediatric patients with cancer before and after administration of etoposide. Five of 27 tested drugs (50-100 μmol/L) inhibited hOCTN2-mediated carnitine uptake by 42% to 85% (P < 0.001). Of these inhibitors, etoposide was itself a transported substrate of hOCTN2 and mOctn2. Etoposide uptake by hOCTN2 was reversed in the presence of excess carnitine. This competitive inhibitory mechanism was confirmed in an in silico molecular docking analysis. In addition, etoposide inhibited the transcellular apical-to-basolateral flux of carnitine in kidney cells. Etoposide was also associated with a significant urinary loss of carnitine in mice (~1.5-fold) and in patients with cancer (~2.4-fold). Collectively, these findings indicate that etoposide can inhibit hOCTN2 function, potentially disturb carnitine homeostasis, and that this phenomenon can contribute to treatment-related toxicities.
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Registered trials
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.