ArticleApoptosis : an international journal on programmed cell death2021
Synergistic inhibitory effect of berberine and icotinib on non-small cell lung cancer cells via inducing autophagic cell death and apoptosis.
Article in Apoptosis : an international journal on programmed cell death, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Cellular and Molecular Mechanisms of Berberine in Cancer Therapy: Recent Advances.Archiv der Pharmazie · 2026Review
- Berberine as a Multifunctional Adjuvant in Cancer Therapy: Mechanistic Insights, Nanotechnological Strategies, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Recent Update Targeting Autophagy-Apoptosis Crosstalk Using Bioactive Natural Products for Ovarian Cancer Treatment.Biomedicines · 2026Review
- Targeting regulated cell death pathways in lung cancer: mechanisms, therapeutic strategies, and clinical translation.Frontiers in immunology · 2026Review
- Natural compounds for non-small cell lung cancer treatment: focus on the EGFR signaling pathway.Frontiers in pharmacology · 2026Review
- Understanding the immunomodulatory mechanisms for natural products that overcome tumor chemoresistance to platinum-based cancer drugs and other treatments.Frontiers in pharmacology · 2026Review
- Non-small cell lung cancer after EGFR-TKI resistance: from drug resistance mechanisms to precision interventions.Frontiers in pharmacology · 2026Review
- Berberine pharmacological properties and therapeutic potential across cancer, digestive, metabolic, cardiovascular, and neurological diseases: an update review.EXCLI journal · 2025Review
- Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Transforming Cancer Treatment with Nanotechnology: The Role of Berberine as a Star Natural Compound.International journal of nanomedicine · 2024Review
- Neuroprotective Properties of Berberine: Molecular Mechanisms and Clinical Implications.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective.Biomolecules · 2022Review
- Programmed cell death lives.Apoptosis : an international journal on programmed cell death · 2022Article
- Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review.Molecules (Basel, Switzerland) · 2022Review
- Berberine induces non-small cell lung cancer apoptosis via the activation of the ROS/ASK1/JNK pathway.Annals of translational medicine · 2022Article
- Natural biomolecules and derivatives as anticancer immunomodulatory agents.Frontiers in immunology · 2022Review
- Apoptosis Induction, a Sharp Edge of Berberine to Exert Anti-Cancer Effects, Focus on Breast, Lung, and Liver Cancer.Frontiers in pharmacology · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Resistance to epidermal growth factor receptor-tyrosin kinase inhibitors (TKIs, e.g. icotinib) remains a major clinical challenge. Non-small cell lung cancer patients with wild-type EGFR and/or K-RAS mutation are primary resistance to EGFR-TKIs. Berberine has been found to have potent anticancer activities via distinct molecular mechanism. In this study, we sought to investigate the therapeutic utility of BBR in combination with icotinib to overcome icotinib resistance in NSCLC cells, and explore the molecular mechanism of synergism of icotinib and BBR to EGFR-resistant NSCLC cells. We used the two EGFR-resistant NSCLC cell lines H460 and H1299 for testing the inhibitory effect of icotinib and/or BBR on them. Moreover, xenograft mouse model was applied for assessing the anti-tumor activities of BBR and icotinib in combination. Results showed that BBR and icotinib have a synergistic inhibitory effect on H460 and H1299 cells through induction of autophagic cell death and apoptosis. Accordingly, the anti-cancer effect of BBR plus icotinib was further confirmed in the NSCLC xenograft mouse models. Combination of BBR and icotinib significantly inhibited the protein expression and the activity of EGFR by inducing autophagic EGFR degradation. BBR plus icotinib resulted in intracellular ROS accumulation, which could mediated autophagy and apoptosis and involved in the suppression of cell migration and invasion. In conclusions, combination application of BBR and icotinib could be an effective strategy to overcome icotinib resistance in the treatment of NSCLC.
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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.