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Salinomycin induces...
Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity : Differences between primary and cancer cells
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- Jangamreddy, Jaganmohan (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Ghavami, Saeid (författare)
- University of Manitoba, Winnipeg, Canada
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- Grabarek, Jerzy (författare)
- Pomeranian Medical University, Szczecin, Poland
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- Kratz, Gunnar (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Regenerativ medicin,Hälsouniversitetet,Hand- och plastikkirurgiska kliniken US
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- Wiechec, Emilia (författare)
- Linköpings universitet,Cellbiologi,Regenerativ medicin,Hälsouniversitetet
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- Fredriksson, Bengt-Arne (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Rao, Rama K. (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Cieślar-Pobuda, Artur (författare)
- Linköpings universitet,Cellbiologi,Regenerativ medicin,Hälsouniversitetet
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- Panigrahi, Soumya (författare)
- Lerner Research Institute, Cleveland, OH, USA
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- Łos, Marek (författare)
- Linköpings universitet,Cellbiologi,Regenerativ medicin,Hälsouniversitetet
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(creator_code:org_t)
- Elsevier BV, 2013
- 2013
- Engelska.
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier BV. - 0167-4889 .- 1879-2596. ; 1833:9, s. 2057-2069
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https://doi.org/10.1...
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https://liu.diva-por... (primary) (Raw object)
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The molecular mechanism of Salinomycin's toxicity is not fully understood. Various studies reported that Ca2 +, 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- cancer stem cells; mitofusin; mitophagy; mTOR; PGC1α; salinomycin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Jangamreddy, Jag ...
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Ghavami, Saeid
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Grabarek, Jerzy
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Kratz, Gunnar
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Wiechec, Emilia
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Fredriksson, Ben ...
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visa fler...
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Rao, Rama K.
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Cieślar-Pobuda, ...
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Panigrahi, Soumy ...
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Łos, Marek
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visa färre...
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