Bitte benutzen Sie diese Kennung, um auf die Ressource zu verweisen: http://doi.org/10.25358/openscience-810
Autoren: Wiench, Benjamin
Eichhorn, Tolga
Paulsen, Malte
Efferth, Thomas
Titel: Shikonin directly targets mitochondria and causes mitochondrial dysfunction in cancer cells
Online-Publikationsdatum: 31-Jan-2013
Sprache des Dokuments: Englisch
Zusammenfassung/Abstract: Chemotherapy is a mainstay of cancer treatment. Due to increased drug resistance and the severe side effects of currently used therapeutics, new candidate compounds are required for improvement of therapy success. Shikonin, a natural naphthoquinone, was used in traditional Chinese medicine for the treatment of different inflammatory diseases and recent studies revealed the anticancer activities of shikonin. We found that shikonin has strong cytotoxic effects on 15 cancer cell lines, including multidrug-resistant cell lines. Transcriptome-wide mRNA expression studies showed that shikonin induced genetic pathways regulating cell cycle, mitochondrial function, levels of reactive oxygen species, and cytoskeletal formation. Taking advantage of the inherent fluorescence of shikonin, we analyzed its uptake and distribution in live cells with high spatial and temporal resolution using flow cytometry and confocal microscopy. Shikonin was specifically accumulated in the mitochondria, and this accumulation was associated with a shikonin-dependent deregulation of cellular Ca(2+) and ROS levels. This deregulation led to a breakdown of the mitochondrial membrane potential, dysfunction of microtubules, cell-cycle arrest, and ultimately induction of apoptosis. Seeing as both the metabolism and the structure of mitochondria show marked differences between cancer cells and normal cells, shikonin is a promising candidate for the next generation of chemotherapy.
DDC-Sachgruppe: 610 Medizin
610 Medical sciences
Veröffentlichende Institution: Johannes Gutenberg-Universität Mainz
Organisationseinheit: FB 09 Chemie, Pharmazie u. Geowissensch.
Veröffentlichungsort: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-810
URN: urn:nbn:de:hebis:77-32616
Version: Published version
Publikationstyp: Zeitschriftenaufsatz
Nutzungsrechte: CC BY
Informationen zu den Nutzungsrechten: https://creativecommons.org/licenses/by/3.0/
Zeitschrift: Evidence-based complementary and alternative medicine
9
Seitenzahl oder Artikelnummer: 1
15
Verlag: Hindawi
Verlagsort: New York, NY
Erscheinungsdatum: 2012
ISSN: 1741-427X
URL der Originalveröffentlichung: http://dx.doi.org/10.1155/2012/726025
DOI der Originalveröffentlichung: 10.1155/2012/726025
Enthalten in den Sammlungen:JGU-Publikationen

Dateien zu dieser Ressource:
  Datei Beschreibung GrößeFormat
Miniaturbild
3261.pdf3.28 MBAdobe PDFÖffnen/Anzeigen