Title |
Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: Differences between primary and cancer cells
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Published in |
Biochimica et Biophysica Acta (BBA), April 2013
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DOI | 10.1016/j.bbamcr.2013.04.011 |
Pubmed ID | |
Authors |
Jaganmohan Reddy Jangamreddy, Saeid Ghavami, Jerzy Grabarek, Gunnar Kratz, Emilia Wiechec, Bengt-Arne Fredriksson, Rama Krishna Rao Pariti, Artur Cieślar-Pobuda, Soumya Panigrahi, Marek J. Łos |
Abstract |
The molecular mechanism of Salinomycin's toxicity is not fully understood. Various studies reported that Ca(2+), cytochrome c, and caspase activation play a role in Salinomycin-induced cytotoxicity. Furthermore, Salinomycin may target Wnt/β-catenin signaling pathway to promote differentiation and thus elimination of cancer stem cells. In this study, we show a massive autophagic response to Salinomycin (substantially stronger than to commonly used autophagic inducer Rapamycin) in prostrate-, breast cancer cells, and to lesser degree in human normal dermal fibroblasts. Interestingly, autophagy induced by Salinomycin is a cell protective mechanism in all tested cancer cell lines. Furthermore, Salinomycin induces mitophagy, mitoptosis and increased mitochondrial membrane potential (∆Ψ) in a subpopulation of cells. Salinomycin strongly, and in time-dependent manner decreases cellular ATP level. Contrastingly, human normal dermal fibroblasts treated with Salinomycin show some initial decrease in mitochondrial mass, however they are largely resistant to Salinomycin-triggered ATP-depletion. Our data provide new insight into the molecular mechanism of preferential toxicity of Salinomycin towards cancer cells, and suggest possible clinical application of Salinomycin in combination with autophagy inhibitors (i.e. clinically-used Chloroquine). Furthermore, we discuss preferential Salinomycins toxicity in the context of Warburg effect. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Croatia | 1 | 1% |
United States | 1 | 1% |
Unknown | 91 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 22 | 24% |
Student > Master | 12 | 13% |
Researcher | 10 | 11% |
Student > Bachelor | 9 | 10% |
Student > Doctoral Student | 8 | 9% |
Other | 19 | 20% |
Unknown | 13 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 19 | 20% |
Agricultural and Biological Sciences | 16 | 17% |
Medicine and Dentistry | 14 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 11 | 12% |
Chemistry | 5 | 5% |
Other | 12 | 13% |
Unknown | 16 | 17% |