ArticlePloS one2014
Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- The role and implication of autophagy in cholangiocarcinoma.Cell death discovery · 2023Review
- Autolysosomal activation combined with lysosomal destabilization efficiently targets myeloid leukemia cells for cell death.Frontiers in oncology · 2023Article
- Combined Anticancer Effect of Plasma-Activated Infusion and Salinomycin by Targeting Autophagy and Mitochondrial Morphology.Frontiers in oncology · 2021Article
- Effects of salinomycin and niclosamide on small cell lung cancer and small cell lung cancer circulating tumor cell lines.Investigational new drugs · 2020Article
- Primary Human Hepatocytes, but Not HepG2 or Balb/c 3T3 Cells, Efficiently Metabolize Salinomycin and Are Resistant to Its Cytotoxicity.Molecules (Basel, Switzerland) · 2020Article
- Misaponin B Induces G2/M Arrest, Cytokinesis Failure and Impairs Autophagy.BioMed research international · 2020Article
- SB365,Molecules (Basel, Switzerland) · 2019Article
- Parallel damage in mitochondria and lysosomes is an efficient way to photoinduce cell death.Autophagy · 2019Article
- Enhanced anticancer effect of oncostatin M combined with salinomycin in CD133Oncology letters · 2019Article
- New insights into autophagy in hepatocellular carcinoma: mechanisms and therapeutic strategies.American journal of cancer research · 2019Review
- Oxidative Stress-Driven Autophagy acROSs Onset and Therapeutic Outcome in Hepatocellular Carcinoma.Oxidative medicine and cellular longevity · 2019Review
- Article
- Zidovudine-Mediated Autophagy Inhibition Enhances Mitochondrial Toxicity in Muscle Cells.Antimicrobial agents and chemotherapy · 2019Article
- CAGE-miR-140-5p-Wnt1 Axis Regulates Autophagic Flux, Tumorigenic Potential of Mouse Colon Cancer Cells and Cellular Interactions Mediated by Exosomes.Frontiers in oncology · 2019Article
- Review
- Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas.Cancer science · 2018Article
- Autophagy and liver cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2018Review
- Maduramicin induces apoptosis and necrosis, and blocks autophagic flux in myocardial H9c2 cells.Journal of applied toxicology : JAT · 2018Article
- Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review.Journal of experimental & clinical cancer research : CR · 2018Review
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Salinomycin raised hope to be effective in anti-cancer therapies due to its capability to overcome apoptosis-resistance in several types of cancer cells. Recently, its effectiveness against human hepatocellular carcinoma (HCC) cells both in vitro and in vivo was demonstrated. However, the mechanism of action remained unclear. Latest studies implicated interference with the degradation pathway of autophagy. This study aimed to determine the impact of Salinomycin on HCC-autophagy and whether primary human hepatocytes (PHH) likewise are affected. Following exposure of HCC cell lines HepG2 and Huh7 to varying concentrations of Salinomycin (0-10 µM), comprehensive analysis of autophagic activity using western-blotting and flow-cytometry was performed. Drug effects were analyzed in the settings of autophagy stimulation by starvation or PP242-treatment and correlated with cell viability, proliferation, apoptosis induction, mitochondrial mass accumulation and reactive oxygen species (ROS) formation. Impact on apoptosis induction and cell function of PHH was analyzed. Constitutive and stimulated autophagic activities both were effectively suppressed in HCC by Salinomycin. This inhibition was associated with dysfunctional mitochondria accumulation, increased apoptosis and decreased proliferation and cell viability. Effects of Salinomycin were dose and time dependent and could readily be replicated by pharmacological and genetic inhibition of HCC-autophagy alone. Salinomycin exposure to PHH resulted in transient impairment of synthesis function and cell viability without apoptosis induction. In conclusion, our data suggest that Salinomycin suppresses late stages of HCC-autophagy, leading to impaired recycling and accumulation of dysfunctional mitochondria with increased ROS-production all of which are associated with induction of apoptosis.
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Registered trials
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.