ArticleOncotarget2015
Glycyrrhetinic acid induces cytoprotective autophagy via the inositol-requiring enzyme 1α-c-Jun N-terminal kinase cascade in non-small cell lung cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Terpenoids as modulators of autophagy-senescence crosstalk in lung cancer.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Mechanism of action of alkaloids inOncology letters · 2026Article
- Insights Into Effects of Natural Bioactive Components on Inflammatory Diseases in Respiratory Tract.Phytotherapy research : PTR · 2025Review
- Epilepsy and autophagy modulators: a therapeutic split.Autophagy · 2025Review
- Bioactive components and delivery strategies of food-medicine homologous substances in lung cancer therapy: current advances and clinical translation.Frontiers in nutrition · 2025Review
- Endoplasmic reticulum stress in non-small cell lung cancer.American journal of cancer research · 2025Review
- Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator.Molecular medicine (Cambridge, Mass.) · 2023Review
- Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats.Molecules (Basel, Switzerland) · 2022Article
- The Effect of Terpenoid Natural Chinese Medicine Molecular Compound on Lung Cancer Treatment.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Glycyrrhetinic acid binds to the conserved P-loop region and interferes with the interaction of RAS-effector proteins.Acta pharmaceutica Sinica. B · 2019Article
- 18β-Glycyrrhetinic-acid-mediated unfolded protein response induces autophagy and apoptosis in hepatocellular carcinoma.Scientific reports · 2018Article
- [Glycyrrhetinic acid selectively inhibits proliferation of hepatocellular carcinoma cells in vitro].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- Glycyrrhetinic Acid Antagonizes Pressure-Induced Venous Remodeling in Mice.Frontiers in physiology · 2018Article
- Article
- Trehalose protects against cadmium-induced cytotoxicity in primary rat proximal tubular cells via inhibiting apoptosis and restoring autophagic flux.Cell death & disease · 2017Article
- Blocking autophagy enhances the apoptotic effect of 18β-glycyrrhetinic acid on human sarcoma cells via endoplasmic reticulum stress and JNK activation.Cell death & disease · 2017Article
- Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.Redox biology · 2017Article
- [Advances in the Research of the Regulation of Chinese Traditional Medicine Monomer and Its Derivatives on Autophagy in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2017Review
- Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2017Review
- Autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic reticulum stress and oxidative stress.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycerrhetinic acid (GA), one of the main bioactive constituents of Glycyrrhiza uralensis Fisch, exerts anti-cancer effects on various cancer cells. We confirmed that GA inhibited cell proliferation and induced apoptosis in non-small cell lung cancer A549 and NCI-H1299 cells. GA also induced expression of autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and punta formation of green fluorescent protein microtubule-associated protein light-chain 3. We further proved that expression of GA-increased autophagy marker was attributed to activation instead of suppression of autophagic flux. The c-jun N-terminal kinase (JNK) pathway was activated after incubation with GA. Pretreatment with the JNK inhibitor SP600125 or silencing of the JNK pathway by siRNA of JNK or c-jun decreased GA-induced autophagy. The endoplasmic reticulum (ER) stress responses were also apparently stimulated by GA by triggering the inositol-requiring enzyme 1α (IRE1α) pathway. The GA-induced JNK pathway activation and autophagy were decreased by IRE1α knockdown, and inhibition of autophagy or the JNK cascade increased GA-stimulated IRE1α expression. In addition, GA-induced cell proliferative inhibition and apoptosis were increased by inhibition of autophagy or the JNK pathway. Our study was the first to demonstrate that GA induces cytoprotective autophagy in non-small cell lung cancer cells by activating the IRE1α-JNK/c-jun pathway. The combined treatment of autophagy inhibitors markedly enhances the anti-neoplasmic activity of GA. Such combination shows potential as a strategy for GA or GA-contained prescriptions in cancer therapy.
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