ArticleOncotarget2016
Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- STAT3 exerts pro-tumor and anti-autophagy roles in cervical cancer.Diagnostic pathology · 2022Article
- The complex relationship between multiple drug resistance and the tumor pH gradient: a review.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming.Nature communications · 2021Article
- Combined Anticancer Effect of Plasma-Activated Infusion and Salinomycin by Targeting Autophagy and Mitochondrial Morphology.Frontiers in oncology · 2021Article
- Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications.Frontiers in oncology · 2021Review
- Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways.Immunology · 2020Review
- A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics.International journal of molecular sciences · 2020Review
- Therapeutic Targeting of Cancer Stem Cells: Integrating and Exploiting the Acidic Niche.Frontiers in oncology · 2019Review
- Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review.Journal of experimental & clinical cancer research : CR · 2018Review
- Article
- A drug screening assay on cancer cells chronically adapted to acidosis.Cancer cell international · 2018Article
- An agent-based model of triple-negative breast cancer: the interplay between chemokine receptor CCR5 expression, cancer stem cells, and hypoxia.BMC systems biology · 2017Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sustained autophagy contributes to the metabolic adaptation of cancer cells to hypoxic and acidic microenvironments. Since cells in such environments are resistant to conventional cytotoxic drugs, inhibition of autophagy represents a promising therapeutic strategy in clinical oncology. We previously reported that the efficacy of hydroxychloroquine (HCQ), an autophagy inhibitor under clinical investigation is strongly impaired in acidic tumor environments, due to poor uptake of the drug, a phenomenon widely associated with drug resistance towards many weak bases. In this study we identified salinomycin (SAL) as a potent inhibitor of autophagy and cytotoxic agent effective on several cancer cell lines under conditions of transient and chronic acidosis. Since SAL has been reported to specifically target cancer-stem cells (CSC), we used an established model of breast CSC and CSC derived from breast cancer patients to examine whether this specificity may be associated with autophagy inhibition. We indeed found that CSC-like cells are more sensitive to autophagy inhibition compared to cells not expressing CSC markers. We also report that the ability of SAL to inhibit mammosphere formation from CSC-like cells was dramatically enhanced in acidic conditions. We propose that the development and use of clinically suitable SAL derivatives may result in improved autophagy inhibition in cancer cells and CSC in the acidic tumor microenvironment and lead to clinical benefits.
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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.