ArticleInternational journal of molecular medicine2017
Betulinic acid induces apoptosis by regulating PI3K/Akt signaling and mitochondrial pathways in human cervical cancer cells.
Article in International journal of molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
- Research advances in the application of betulinic acid for anti-inflammatory and anti-tumour therapy.Chinese medicine · 2026Review
- Combination Therapy with Betulinic Acid and TRAIL Increases ROS-Dependent Cytotoxicity and Inhibits PI3K/Akt Signaling in Human Bladder Cancer Cells.Biomolecules & therapeutics · 2026Article
- Betulinic acid isolated fromHistology and histopathology · 2026Article
- The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.International journal of molecular sciences · 2026Review
- An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance.Cancers · 2026Review
- Betulinic Acid and Betulin Suppress Melanoma Growth by Modulating Apoptosis and Autophagy via PI3K/AKT/mTOR and MAPK Pathways.International journal of molecular sciences · 2026Article
- Impact of plant-based interventions on gynecological cancers: a narrative review of mechanistic interplays and clinical evidence.Frontiers in molecular medicine · 2026Review
- Modulation of Autophagy by Ursolic and Betulinic Acids: Distinct Cytotoxic and Membrane-Disruption in Malignant and Nonmalignant Cells.Cell biology international · 2025Article
- Betulin: a novel triterpenoid anti-cancerous agent targeting cervical cancer through epigenetic proteins.Molecular diversity · 2025Article
- Plant-based secondary metabolites as natural remedies: a comprehensive review on terpenes and their therapeutic applications.Frontiers in pharmacology · 2025Review
- Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generation.Medical oncology (Northwood, London, England) · 2024Article
- The Influence of Betulin Derivatives EB5 and ECH147 on the Expression of Selected TGFβ Superfamily Genes,Current issues in molecular biology · 2023Article
- Enhanced Anti-cancer Potency Using a Combination of Oleanolic Acid and Maslinic Acid to Control Treatment Resistance in Breast Cancer.Advanced pharmaceutical bulletin · 2023Article
- Betulinic Acid-Brosimine B Hybrid Compound Has a Synergistic Effect with Imatinib in Chronic Myeloid Leukemia Cell Line, Modulating Apoptosis and Autophagy.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Targeting the Interplay of Autophagy and ROS for Cancer Therapy: An Updated Overview on Phytochemicals.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Research Progress on Application of Inonotus obliquus in Diabetic Kidney Disease.Journal of inflammation research · 2023Review
- The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential.Molecules (Basel, Switzerland) · 2022Article
- Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry.Molecules (Basel, Switzerland) · 2022Article
- Secondary Metabolites with Biomedical Applications from Plants of the Sarraceniaceae Family.International journal of molecular sciences · 2022Review
- Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia-Reperfusion.International journal of molecular sciences · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Betulinic acid (BA), a potential anticancer compound, could induce apoptosis in human cervical cancer (HeLa) cells, but its mechanism has yet to be fully elucidated. The present study was focused on deciphering the detailed molecular mechanism of BA-induced apoptosis. In the present study, results indicated that BA was highly effective against HeLa cells via induction of time-dependent apoptosis, and the authors demonstrated that the BA treatment acted through downregulating a phosphatidylinositol 3-kinase (PI3K) subunit and suppressing the Akt phosphorylation at Thr308 and Ser473 after increasing the generation of intracellular reactive oxygen species. Then, BA induced cell cycle arrest at the G0/G1 phase, which was consistent with the cell cycle-related protein results in which BA significantly enhanced the expression of p27Kip and p21Waf1/Cip1 in HeLa cells. This target-specific inhibition was associated with mitochondrial apoptosis, as reflected by the increased expression of Bad and caspase-9, the generation of reactive oxygen species (ROS) and the decline in mitochondrial membrane potential. Moreover, preincubation of the cells with glutathione (antioxidant) blocked the process of apoptosis, prevented the phosphorylation of downstream substrates. These results established that ROS acted as a key factor to effect apoptosis by BA treatment in HeLa cells. Therefore, these findings demonstrated that BA induced apoptosis in HeLa cells by downregulating the expression of PI3K/Akt signaling molecules via ROS, and triggering a mitochondrial 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.