ArticleTranslational oncology2021
LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence.
Article in Translational oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- ERα36 is associated with SLC7A5/LAT1 expression, cervical cancer progression, and BNCT response: a translational study.Frontiers in oncology · 2026Article
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Sustained reductions in valine and isoleucine mediate anti-cancer pharmacological effects of inhibiting amino acid transporter LAT1 in cancer cells.Cancer & metabolism · 2025Article
- Relationship between amino acid transporter activity and radioactive iodine therapy efficacy in differentiated thyroid cancer.Oncology reports · 2025Article
- Astatine-211-Labeled Therapy Targeting Amino Acid Transporters: Overcoming Drug Resistance in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Non-Canonical, Strongly Selective Protein Disulfide Isomerases as Anticancer Therapeutic Targets.Biomolecules · 2025Review
- Targeting emerging amino acid dependencies and transporters in cancer therapy.Frontiers in pharmacology · 2025Review
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches.Pharmaceutics · 2024Review
- Insights into the Transport Cycle of LAT1 and Interaction with the Inhibitor JPH203.International journal of molecular sciences · 2023Article
- Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer.Journal of personalized medicine · 2023Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
L-type amino acid transporter 1 (LAT1) is important for transporting neutral amino acids into cells. LAT1 expression is correlated with cancer malignancy, suggesting that LAT1 is a promising target for cancer therapy. JPH203, a potential novel drug targeting LAT1, has been shown to suppress tumor growth in various cancer cell lines. However, a combination study of JPH203 and radiation therapy has not been reported. Here, we examined the effects of JPH203 on radiosensitivity after irradiation in A549 and MIA Paca-2 cells. We showed that X-irradiation increased cellular neutral amino acid uptake via LAT1 in both cell lines. JPH203 inhibited the radiation-induced increase in neutral amino acid uptake. We demonstrated that JPH203, at minimally toxic concentrations, significantly sensitized cancer cells to radiation. JPH203 significantly downregulated mTOR activity and enhanced cellular senescence post-irradiation without reducing ATP and GSH levels. These results indicate that LAT1 inhibition by JPH203 sensitizes cancer cells to radiation by enhancing cellular senescence via mTOR downregulation. Thus, JPH203 may be a potent anti-cancer drug in combination with radiation therapy.
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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.