ArticleAmerican journal of translational research2019
Betulinic acid induces autophagy-mediated apoptosis through suppression of the PI3K/AKT/mTOR signaling pathway and inhibits hepatocellular carcinoma.
Article in American journal of translational research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Separation, Structural Elucidation, and Anticancer Activity of a Diastereoisomer of Betulonic Acid-Zidovudine Conjugates.ACS omega · 2026Article
- A review of PI3K/AKT/mTOR inhibitors from traditional Chinese medicine: potential and perspective for activated phosphoinositide 3-kinase δ syndrome.Orphanet journal of rare diseases · 2026Review
- Betulinic acid is associated with miR-21 modulation, apoptosis and redox changes in breast cancer cells: an in vitro and in silico study.Scientific reports · 2026Article
- Combination Therapy with Betulinic Acid and TRAIL Increases ROS-Dependent Cytotoxicity and Inhibits PI3K/Akt Signaling in Human Bladder Cancer Cells.Biomolecules & therapeutics · 2026Article
- The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.International journal of molecular sciences · 2026Review
- Modulation of Autophagy by Ursolic and Betulinic Acids: Distinct Cytotoxic and Membrane-Disruption in Malignant and Nonmalignant Cells.Cell biology international · 2025Article
- Computational Network Pharmacology, Molecular Docking, and Molecular Dynamics to Decipher Natural Compounds ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- Plant-based secondary metabolites as natural remedies: a comprehensive review on terpenes and their therapeutic applications.Frontiers in pharmacology · 2025Review
- The activity of pyrazolo[4,3-Journal of enzyme inhibition and medicinal chemistry · 2024Article
- A recent update on the connection between dietary phytochemicals and skin cancer: emerging understanding of the molecular mechanism.Annals of medicine and surgery (2012) · 2024Review
- Review
- Combination of betulinic acid and EGFR-TKIs exerts synergistic anti-tumor effects against wild-type EGFR NSCLC by inducing autophagy-related cell death via EGFR signaling pathway.Respiratory research · 2024Article
- Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma.Heliyon · 2024Review
- Targeting cell death mechanisms: the potential of autophagy and ferroptosis in hepatocellular carcinoma therapy.Frontiers in immunology · 2024Review
- Synthesis, Pharmacological Properties, and Potential Molecular Mechanisms of Antitumor Activity of Betulin and Its Derivatives in Gastrointestinal Cancers.Pharmaceutics · 2023Review
- Anticancer effect of terpenes: focus on malignant melanoma.Pharmacological reports : PR · 2023Review
- miR-210 promotes hepatocellular carcinoma progression by modulating macrophage autophagy through PI3K/AKT/mTOR signaling.Biochemical and biophysical research communications · 2023Article
- Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Modulation of Cell Death Pathways for Cellular Protection and Anti-Tumoral Activity: The Role ofInternational journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Betulinic acid (BA) is a pentacyclic triterpenoid compound that widely exists in Chinese herbal medicine, and it has remarkable biological activity. However, the involved molecular targets and mechanisms of BA are still ambiguous. Here, we aim to validate the preventive effects and molecular mechanisms of BA against hepatocellular carcinoma via related experiments. We extracted the 2D and 3D structure of BA from the PubChem database. MTT assay and colony formation assay were used to determine the anti-proliferation and cytotoxicity of BA using in vitro cell models. Hoechst 33258 staining was used to investigate the extent of apoptosis after BA treatment. Western blot and immunofluorescence experiments were used to evaluate apoptosis-related and autophagy-related proteins and molecular mechanisms. We demonstrated that BA significantly inhibited cell proliferation in HepG2 and SMMC-7721 hepatocellular carcinoma cells, but with little cytotoxicity effects on l-02 normal liver cells. We further determined that the hepatocellular carcinoma prevention effects of BA were closely correlated with apoptosis and autophagy. Furthermore, our data indicated that BA-induced autophagy has a protective effect against cancer cell proliferation and promotes cell apoptosis. Additionally, apoptosis and autophagy were induced by BA through suppression of the PI3K/AKT/mTOR signaling pathway. Collectively, our study provides experimental evidence that BA inhibits cell proliferation and induces cell apoptosis and autophagy via suppressing the PI3K/AKT/mTOR pathway. Additionally, BA is a safe and effective herbal medicine compound that can be used for the prevention of hepatocellular carcinoma growth, and may be a potential therapeutic strategy against hepatocellular carcinoma.
Indexed as
Identifiers
31814899PMC6895530W2997349006What 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.