ArticleCell death & disease2017
Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop.
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 42 papers.
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Who cites it
42 citing papers in PubMed, 83 citations in OpenAlex.
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- Sesquiterpene Lactones as Promising Phytochemicals to Cease Metastatic Propagation of Cancer.Biomolecules · 2025Review
- Nrf2 in human cancers: biological significance and therapeutic potential.American journal of cancer research · 2024Review
- A proteomic landscape of pharmacologic perturbations for functional relevance.Journal of pharmaceutical analysis · 2024Article
- The Crosstalk between Autophagy and Nrf2 Signaling in Cancer: from Biology to Clinical Applications.International journal of biological sciences · 2024Review
- The role and implication of autophagy in cholangiocarcinoma.Cell death discovery · 2023Review
- Polyphyllin D punctures hypertrophic lysosomes to reverse drug resistance of hepatocellular carcinoma by targeting acid sphingomyelinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Inhibition of Calcium-Sensing Receptor Alleviates Chronic Intermittent Hypoxia-Induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway.Molecular neurobiology · 2023Article
- Review
- Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway.Redox biology · 2022Review
- Deoxyelephantopin and Its Isomer Isodeoxyelephantopin: Anti-Cancer Natural Products with Multiple Modes of Action.Molecules (Basel, Switzerland) · 2022Review
- MANF InhibitsOxidative medicine and cellular longevity · 2022Article
- Unfolding the role of autophagy in the cancer metabolism.Biochemistry and biophysics reports · 2021Article
- Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review).International journal of oncology · 2021Review
- MEST promotes lung cancer invasion and metastasis by interacting with VCP to activate NF-κB signaling.Journal of experimental & clinical cancer research : CR · 2021Article
- LC-ToF-ESI-MS Patterns of Hirsutinolide-like Sesquiterpenoids Present in theMolecules (Basel, Switzerland) · 2021Article
- Inhibiting autophagy enhances sulforaphane-induced apoptosisActa pharmaceutica Sinica. B · 2021Article
- TRIM21-regulated Annexin A2 plasma membrane trafficking facilitates osteosarcoma cell differentiation through the TFEB-mediated autophagy.Cell death & disease · 2021Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isodeoxyelephantopin (ESI), isolated from Elephantopus scaber L. has been reported to exert anticancer effects. In this study, we aimed to investigate whether and how cancer cells exert protective responses against ESI treatment. Confocal fluorescence microscopy showed that ESI significantly induced autophagy flux in the lung cancer cells expressing mCherry-EGFP-LC3 reporter. Treatment of the cells with ESI increased the expression levels of the autophagy markers including LC3-II, ATG3 and Beclin1 in a dose-dependent manner. Pretreatment with autophagy inhibitor 3-methyladenine (3-MA) not only attenuated the effects of ESI on autophagy, but also enhanced the effects of ESI on cell viability and apoptosis. Mechanistically, the SILAC quantitative proteomics coupled with bioinformatics analysis revealed that the ESI-regulated proteins were mainly involved in Nrf2-mediated oxidative stress response. We found that ESI induced the nuclear translocation of Nrf2 for activating the downstream target genes including HO-1 and p62 (SQSTM1). More importantly, ESI-induced p62 could competitively bind with Keap1, and releases Nrf2 to activate downstream target gene p62 as a positive feedback loop, therefore promoting autophagy. Furthermore, knockdown of Nrf2 or p62 could abrogate the ESI-induced autophagy and significantly enhanced the anticancer effect of ESI. Taken together, we demonstrated that ESI can sustain cell survival by activating protective autophagy through Nrf2-p62-keap1 feedback loop, whereas targeting this regulatory axis combined with ESI treatment may be a promising strategy for anticancer therapy.
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