ArticleCell death & disease2017
Overaccumulation of p53-mediated autophagy protects against betulinic acid-induced apoptotic cell death in colorectal cancer cells.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Modulation of Autophagy by Ursolic and Betulinic Acids: Distinct Cytotoxic and Membrane-Disruption in Malignant and Nonmalignant Cells.Cell biology international · 2025Article
- Enhancing the Pharmacological Properties of Triterpenes Through Acetylation: An Anticancer and Antioxidant Perspective.Molecules (Basel, Switzerland) · 2025Article
- Metabolic Reprogramming of Urothelial Carcinoma-A Theragnostic Target for Betulinic Acid.International journal of molecular sciences · 2025Article
- The Therapeutic Effects of Bioactive Compounds on Colorectal Cancer via PI3K/Akt/mTOR Signaling Pathway: A Critical Review.Food science & nutrition · 2024Review
- Therapeutic Potential of Terpenoids in Cancer Treatment: Targeting Mitochondrial Pathways.Cancer reports (Hoboken, N.J.) · 2024Review
- Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo.Journal of natural medicines · 2024Article
- 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
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- EVA1A, a novel and promising prognostic biomarker in colorectal cancer.Frontiers in oncology · 2024Article
- Novel triphenylphosphonium amphiphilic conjugates of glycerolipid type: synthesis, cytotoxic and antibacterial activity, and targeted cancer cell delivery.RSC medicinal chemistry · 2023Article
- SESN2 Knockdown Increases Betulinic Acid-Induced Radiosensitivity of Hypoxic Breast Cancer Cells.Cells · 2022Article
- 6,6'-((Methylazanedyl)bis(methylene))bis(2,4-dimethylphenol) Induces Autophagic Associated Cell Death through mTOR-Mediated Autophagy in Lung Cancer.Molecules (Basel, Switzerland) · 2022Article
- Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II).International journal of molecular sciences · 2022Review
- How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Autophagy in Cancer: A Metabolic Perspective.Sub-cellular biochemistry · 2022Review
- Terpenoids' anti-cancer effects: focus on autophagy.Apoptosis : an international journal on programmed cell death · 2021Review
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- Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.International journal of molecular sciences · 2021Review
- Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential.Molecules (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the AKT-MTOR signaling pathway. Inhibition of autophagy by either administration of autophagic inhibitor chloroquine or siRNA-mediated knockdown of ATG5 could augment BA-induced apoptotic cell death as well as inhibition of cell proliferation. Moreover, we found that p53 was firstly activated by short exposure to BA and then was rapidly degraded via the ubiquitin-mediated degradation pathway in both wtp53 and mutp53 CRC cells. Notably, more preferential cytotoxicity of BA was obtained in mutp53 cells (IC50 values: HT29, 125 μM; SW480, 58 μM) rather than wtp53 cells (IC50 values: HCT116, 178 μM). Further experiments demonstrated that siRNA-mediated p53 knockdown attenuated BA-induced autophagy, and forced overexpression of p53 augmented BA-induced autophagy, indicating that p53-enhanced BA-induced autophagy. Moreover, BA enhanced the sensitivity of mutp53 cells to chemotherapy drugs such as 5-FU and ADR by degradation of mutp53. Overall, our study proved that BA could induce CRC cell death by inducing apoptosis and reduce the overaccumulation of BA-induced protective autophagy by degrading wtp53 and mutp53 dependent on the ubiquitin-mediated degradation pathway to achieve killer effect, suggesting that BA might serve as a novel desirable drug for mutp53 cancer therapy.
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