ArticleMetabolites2019
Delta-Tocotrienol Modulates Glutamine Dependence by Inhibiting ASCT2 and LAT1 Transporters in Non-Small Cell Lung Cancer (NSCLC) Cells: A Metabolomic Approach.
Article in Metabolites, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Review
- The role of abnormal amino acid metabolism in the occurrence and development of tumors.Frontiers in oncology · 2026Review
- Significance of Vitamins A and E in Cancer Progression and Prevention.International journal of molecular sciences · 2025Review
- Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer.Journal of advanced research · 2025Article
- Metabolic reprogramming and therapeutic targeting in non-small cell lung cancer: emerging insights beyond the Warburg effect.Frontiers in oncology · 2025Review
- SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer.Oncology letters · 2025Article
- MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression.The clinical respiratory journal · 2024Article
- Glutaminolysis and peripheral CD4Frontiers in immunology · 2023Review
- The Involvement of Long Non-Coding RNAs in Glutamine-Metabolic Reprogramming and Therapeutic Resistance in Cancer.International journal of molecular sciences · 2022Review
- Contribution of LAT1-4F2hc in Urological Cancers via Toll-like Receptor and Other Vital Pathways.Cancers · 2022Review
- The putative role of gut microbiota in cancer: Cysteine is a pivotal coin.Frontiers in gastroenterology (Lausanne, Switzerland) · 2022Review
- The role of the glutamine transporter ASCT2 in antineoplastic therapy.Cancer chemotherapy and pharmacology · 2021Review
- LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression.Biomedicines · 2021Review
- ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation.Cancers · 2021Review
- Review
- Therapeutic Potential of Glutamine Pathway in Lung Cancer.Frontiers in oncology · 2021Review
- Circular RNA circ-LDLRAD3 serves as an oncogene to promote non-small cell lung cancer progression by upregulating SLC1A5 through sponging miR-137.RNA biology · 2020Article
- Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas.Biomolecules · 2020Review
- Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols.Molecular carcinogenesis · 2020Review
- Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The growth and development of non-small cell lung cancer (NSCLC) primarily depends on glutamine. Both glutamine and essential amino acids (EAAs) have been reported to upregulate mTOR in NSCLC, which is a bioenergetics sensor involved in the regulation of cell growth, cell survival, and protein synthesis. Seen as novel concepts in cancer development, ASCT2 and LAT transporters allow glutamine and EAAs to enter proliferating tumors as well as send a regulatory signal to mTOR. Blocking or downregulating these glutamine transporters in order to inhibit glutamine uptake would be an excellent therapeutic target for treatment of NSCLC. This study aimed to validate the metabolic dysregulation of glutamine and its derivatives in NSCLC using cellular 1H-NMR metabolomic approach while exploring the mechanism of delta-tocotrienol (δT) on glutamine transporters, and mTOR pathway. Cellular metabolomics analysis showed significant inhibition in the uptake of glutamine, its derivatives glutamate and glutathione, and some EAAs in both cell lines with δT treatment. Inhibition of glutamine transporters (ASCT2 and LAT1) and mTOR pathway proteins (P-mTOR and p-4EBP1) was evident in Western blot analysis in a dose-dependent manner. Our findings suggest that δT inhibits glutamine transporters, thus inhibiting glutamine uptake into proliferating cells, which results in the inhibition of cell proliferation and induction of apoptosis via downregulation of the mTOR pathway.
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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.