ArticleMolecules (Basel, Switzerland)2016
Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation.
Article in Molecules (Basel, Switzerland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- From Natural Compound Screening to Myelin-Associated Effects: Identification of Morusin as a Potent Promoter of Oligodendrocyte Differentiation.International journal of molecular sciences · 2026Article
- Cardenolide glycosides sensitize gefitinib-induced apoptosis in non-small cell lung cancer: inhibition of NaNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway.Oncology reports · 2024Article
- Apoptosis-Inducing Effects of Short-Chain Fatty Acids-Rich Fermented Pistachio Milk in Human Colon Carcinoma Cells.Foods (Basel, Switzerland) · 2023Article
- Traditional Chinese medicine reverses cancer multidrug resistance and its mechanism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Comprehensive Multiomic Analysis Identified TUBA1C as a Potential Prognostic Biological Marker of Immune-Related Therapy in Pan-Cancer.Computational and mathematical methods in medicine · 2022Article
- Prognostic biomarker TUBA1C is correlated to immune cell infiltration in the tumor microenvironment of lung adenocarcinoma.Cancer cell international · 2021Article
- Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity.Foods (Basel, Switzerland) · 2021Article
- TUBA1C is a Prognostic Marker in Low-grade Glioma and Correlates with Immune Cell Infiltration in the Tumor Microenvironment.Frontiers in genetics · 2021Article
- Digitoxin inhibits proliferation of multidrug-resistant HepG2 cells through GOncology letters · 2020Article
- Vascular Effects of Avocado Seed Glycosides during Diabetes-induced Endothelial Damage.Cardiovascular & hematological disorders drug targets · 2020Article
- Proscillaridin A exerts anti-tumor effects through GSK3β activation and alteration of microtubule dynamics in glioblastoma.Cell death & disease · 2018Article
- Expression of engrailed homeobox 2 regulates the proliferation, migration and invasion of non-small cell lung cancer cells.Oncology letters · 2018Article
- Proscillaridin A induces apoptosis and suppresses non-small-cell lung cancer tumor growth via calcium-induced DR4 upregulation.Cell death & disease · 2018Article
- Na/K Pump and Beyond: Na/K-ATPase as a Modulator of Apoptosis and Autophagy.Molecules (Basel, Switzerland) · 2017Review
- Sulforaphane-cysteine-induced apoptosis via phosphorylated ERK1/2-mediated maspin pathway in human non-small cell lung cancer cells.Cell death discovery · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.
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