ArticlePloS one2013
Branched chain amino acid suppresses hepatocellular cancer stem cells through the activation of mammalian target of rapamycin.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- High-fat diet reshapes microbial interactions to promote breast cancer stemness via Streptococcus mutans-induced leucine accumulation.Breast cancer research : BCR · 2026Article
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- Angel or demon? The dual role of branched-chain amino acids in chronic inflammatory and injury-related diseases.Frontiers in immunology · 2026Review
- Article
- Microbial Modulation of the Gut-Liver Axis in Autoimmune Liver Diseases.Seminars in liver disease · 2025Review
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- BCAA metabolism in cancer progression and therapy resistance: The balance between fuel and cell signaling.Frontiers in pharmacology · 2025Review
- Deciphering cellular and molecular mechanism of MUC13 mucin involved in cancer cell plasticity and drug resistance.Cancer metastasis reviews · 2024Review
- EPA and DHA promote cell proliferation and enhance activity of the Akt-TOR-S6K anabolic signaling pathway in primary muscle cells of turbot (Scophthalmus maximus L.).Fish physiology and biochemistry · 2024Article
- Review
- Polyploidy and mTOR signaling: a possible molecular link.Cell communication and signaling : CCS · 2024Review
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- BCSCdb: a database of biomarkers of cancer stem cells.Database : the journal of biological databases and curation · 2022Article
- Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy.World journal of stem cells · 2022Review
- Identification of Prognostic Biomarkers in Patients With Malignant Rhabdoid Tumor of the Kidney Based on mTORC1 Signaling Pathway-Related Genes.Frontiers in molecular biosciences · 2022Article
- Combinatorial antitumor effects of amino acids and epigenetic modulations in hepatocellular carcinoma cell lines.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids.Archives of toxicology · 2021Article
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.Frontiers in pharmacology · 2021Review
- Liposomal 2-Methoxyestradiol Nanoparticles for Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiation of cancer stem cells (CSCs) into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR) leads to CSC survival, the effect of branched chain amino acids (BCAAs), an mTOR complex 1 (mTORC1) activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC) cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU) on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb). mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer 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.