ArticleFrontiers in pharmacology2021
Combination Treatment With Inhibitors of ERK and Autophagy Enhances Antitumor Activity of Betulinic Acid in Non-small-Cell Lung Cancer
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Autophagy-Apoptosis Crosstalk in Cancer: Mechanisms, Signaling Pathways, and Therapeutic Targeting.Cancers · 2026Review
- Cisplatin as a Xenobiotic Agent: Molecular Mechanisms of Actions and Clinical Applications in Oncology.Journal of xenobiotics · 2026Review
- Modulation of Autophagy by Ursolic and Betulinic Acids: Distinct Cytotoxic and Membrane-Disruption in Malignant and Nonmalignant Cells.Cell biology international · 2025Article
- The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.Current issues in molecular biology · 2025Review
- Chlorogenic Acid Enhances Beta-Lapachone-Induced Cell Death by Suppressing Autophagy in NQO1-Positive Cancer Cells.Cell biology international · 2025Article
- The Effects of Silibinin Combined With EGFR-TKIs in the Treatment of NSCLC.Cancer medicine · 2025Review
- The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.Pharmaceutics · 2024Review
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- Article
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- Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective.Biomolecules · 2022Review
- Biodegradable and Bioactive Carriers Based on Poly(betulin disuccinate-Pharmaceutics · 2022Article
- Development of a novel cell-based, In-Cell Western/ERK assay system for the high-throughput screening of agonists acting on the delta-opioid receptor.Frontiers in pharmacology · 2022Article
- Gilteritinib Enhances Anti-Tumor Efficacy of CDK4/6 Inhibitor, Abemaciclib in Lung Cancer Cells.Frontiers in pharmacology · 2022Article
- The Effect of Terpenoid Natural Chinese Medicine Molecular Compound on Lung Cancer Treatment.Evidence-based complementary and alternative medicine : eCAM · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of the Ras-ERK signaling pathway drives many important cancer phenotypes, and several inhibitors targeting such pathways are under investigation and/or approved by the FDA as single- or multi-agent therapy for patients with melanoma and non-small-cell lung cancer (NSCLC). Here, we show that betulinic acid (BA), a natural pentacyclic triterpenoid, inhibits cell proliferation, and induces apoptosis and protective autophagy in NSCLC cells. Thus, the cancer cell killing activity of BA is enhanced by autophagy inhibition. Mitogen-activated protein kinases, and especially ERK that facilitates cancer cell survival, are also activated by BA treatment. As such, in the presence of ERK inhibitors (ERKi), lung cancer cells are much more sensitive to BA. However, the dual treatment of BA and ERKi results in increased protective autophagy and AKT phosphorylation. Accordingly, inhibition of AKT has a highly synergistic anticancer effect with co-treatment of BA and ERKi. Notably, autophagy inhibition by hydroxychloroquine (HCQ) increases the response of lung cancer cells to BA in combination with ERKi.
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