ArticlePloS one2015
Immunomodulatory Protein from Ganoderma microsporum Induces Pro-Death Autophagy through Akt-mTOR-p70S6K Pathway Inhibition in Multidrug Resistant Lung Cancer Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 64 citations in OpenAlex.
- Mushrooms as potent autophagy modulators in cancer therapy: Current evidence and therapeutic prospects.Cancer pathogenesis and therapy · 2026Review
- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- rFIP-GMI Suppresses IGF-1-Induced Invasion and Migration in Breast Cancer Cells via PI3K/Akt/β-Catenin Inhibition.Drug development research · 2025Article
- FIP-nha, a fungal immunomodulatory protein fromFood chemistry. Molecular sciences · 2022Article
- Current Advancements in Antitumor Properties and Mechanisms of Medicinal Components in Edible Mushrooms.Nutrients · 2022Review
- Hinokitiol impedes tumor drug resistance by suppressing protein kinase B/mammalian targets of rapamycin axis.Journal of Cancer · 2022Article
- Safety assessment of the fungal immunomodulatory protein fromToxicology reports · 2022Article
- The MicroRNA-Based Strategies to Combat Cancer ChemoresistanceFrontiers in oncology · 2022Review
- Mycomedicine: A Unique Class of Natural Products with Potent Anti-tumour Bioactivities.Molecules (Basel, Switzerland) · 2021Review
- Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells via Autophagy and Apoptosis.Cancer management and research · 2020Article
- Identification and Functional Characterization of a Novel Immunomodulatory Protein FromFrontiers in immunology · 2020Article
- Immunomodulatory Protein fromInternational journal of molecular sciences · 2019Article
- Inhibition of proliferation and migration of melanoma cells by ketoconazole andOncology letters · 2019Article
- Review
- The Effect of Ganoderma Microsporum immunomodulatory proteins on alleviating PMScientific reports · 2019Article
- Thapsigargin induces apoptosis of prostate cancer through cofilin-1 and paxillin.Oncology letters · 2018Article
- Review
- Article
- GMI ablates cancer stemness and cisplatin resistance in oral carcinomas stem cells through IL-6/Stat3 signaling inhibition.Oncotarget · 2017Article
- Autophagy and multidrug resistance in cancer.Chinese journal of cancer · 2017Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance in cancer therapy is an unfavorable prognostic factor in non-small cell lung cancer (NSCLC). Elevation of intracellular calcium level in multidrug resistant (MDR) sublines leads to sensitization of MDR sublines to cell death. We demonstrated that a fungal protein from Ganoderma microsporum, GMI, elevates the intracellular calcium level and reduces the growth of MDR subline via autophagy and apoptosis, regardless of p-glycoprotein (P-gp) overexpression, in mice xenograft tumors. In addition, we examined the roles of autophagy in the death of MDR A549 lung cancer sublines by GMI, thapsigargin (TG) and tunicamycin (TM) in vitro. Cytotoxicity of TG was inhibited by overexpressed P-gp. However, TM-induced death of MDR sublines was independent of P-gp level. Combinations of TG and TM with either docetaxel or vincristine showed no additional cytotoxic effects on MDR sublines. TG- and TM-mediated apoptosis of MDR sublines was demonstrated on Annexin-V assay and Western blot and repressed by pan-caspase inhibitor (Z-VAD-FMK). Treatment of MDR sublines with TG and TM also augmented autophagy with accumulation of LC3-II proteins, breakdown of p62 and formation of acidic vesicular organelles (AVOs). Inhibition of ATG5 by shRNA silencing significantly reduced autophagy and cell death but not apoptosis following TG or TM treatment. GMI treatment inhibited the phosphorylation of Akt/S473 and p70S6K/T389. Interestingly, the phosphorylation of ERK was not associated with GMI-induced autophagy. We conclude that autophagy plays a pro-death role in acquired MDR and upregulation of autophagy by GMI via Akt/mTOR inhibition provides a potential strategy for overcoming MDR in the treatment of lung cancers.
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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.