ArticleApoptosis : an international journal on programmed cell death2020
Hemocompatible LAT1-inhibitor can induce apoptosis in cancer cells without affecting brain amino acid homeostasis.
Article in Apoptosis : an international journal on programmed cell death, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Orientia tsutsugamushi targets lamin A using Ank effectors and alters chromatin to inhibit NF-κB.Communications biology · 2026Article
- Structural basis for pH-responsive amino acid transport via SLC7A4.Nature communications · 2026Article
- The potential of probiotic derivatives of Bacillus coagulans Hammer on induction of apoptosis in colorectal adenocarcinoma cell line in vitro.BMC complementary medicine and therapies · 2025Article
- Article
- Inhibitory effects of Levilactobacillus brevis IBRC-M10790 on apoptosis and inflammation induced by Clostridioides difficile culture supernatant in vitro.Scientific reports · 2025Article
- Targeting LAT1 with JPH203 to reduce TNBC proliferation and reshape suppressive immune microenvironment by blocking essential amino acid uptake.Amino acids · 2025Article
- Multiple roles of branched-chain amino acid metabolism in tumour progression.Journal of biomedical science · 2025Review
- Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis.Molecular medicine (Cambridge, Mass.) · 2025Article
- SLC7 transporters at the crossroads of amino acid metabolism and diabetes pathophysiology: insights and therapeutic perspectives.Frontiers in nutrition · 2025Review
- Multi-omics analysis reveals phenylalanine enhance mitochondrial function and hypoxic endurance via LKB1/AMPK activation.Journal of translational medicine · 2024Article
- BCKDK modification enhances the anticancer efficacy of CAR-T cells by reprogramming branched chain amino acid metabolism.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- Crosstalk between metabolism and cell death in tumorigenesis.Molecular cancer · 2024Review
- Transporter-Mediated Drug Delivery.Molecules (Basel, Switzerland) · 2023Review
- Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer.Frontiers in oncology · 2023Review
- Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers.International journal of molecular sciences · 2022Review
- Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery.Pharmaceutical research · 2022Review
- Functional Characterization of the Solute Carrier LAT-1 (SLC7A5/SLC2A3) in Human Brain Capillary Endothelial Cells with Rapid UPLC-MS/MS Quantification of Intracellular Isotopically Labelled L-Leucine.International journal of molecular sciences · 2022Article
- Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo.International journal of molecular sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased amounts of amino acids are essential for cancer cells to support their sustained growth and survival. Therefore, inhibitors of amino acid transporters, such as L-type amino acid transporter 1 (LAT1) have been developed. In this study, a previously reported LAT1-inhibitor (KMH-233) was studied for its hemocompatibility and toxicity towards human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (AoSMCs). Furthermore, the cytotoxic effects against human breast adenocarcinoma cells (MCF-7) and its ability to affect mammalian (or mechanistic) target of rapamycin (mTOR) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling were evaluated. Moreover, the effects of this inhibitor to modulate LAT1 function on the cell surface and the brain amino acid homeostasis were evaluated after intraperitoneal (i.p.) administration of LAT1-inhibitor (23 µmol/kg) in mice. The results showed that LAT1-inhibitor (KMH-233) is hemocompatible at concentrations below 25 µM and it does not affect coagulation in plasma. However, it can reduce the total protein amount of mTOR and NF-κB, resulting in increased apoptosis in LAT1-expressing cancer cells. Most importantly, the inhibitor did not affect mouse brain levels of L-Leu, L-Tyr or L-Trp or modulate the function of LAT1 on the MCF-7 cell surface. Therefore, this inhibitor can be considered as a safe but effective anti-cancer agent. However, due to the compensative mechanism of cancer cells for their increased amino acid demand, this compound is most effective inducing apoptosis when used in combinations with other chemotherapeutics, such as protease inhibitor, bestatin, as demonstrated in this study.
Indexed as
Identifiers
What OpenQuestion holds
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.