Shikonin causes cancer cell death by inducing mitochondria! dysfunction

Publication type:
Conference
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000209701602491&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1158/1538-7445.AM2012-4662
eISSN
1538-7445
Externe Identifier
  • Clarivate Analytics Document Solution ID: V43SR
ISSN
0008-5472
Zeitschrift
CANCER RESEARCH
Datum der Veröffentlichung
2012
Status
Published
Titel
Shikonin causes cancer cell death by inducing mitochondria! dysfunction
Ausgabe der Zeitschrift
72

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title> <jats:p>Shikonin, a naturally occurring napthoquinone, has been used in herbal formulations for the treatment of several inflammatory diseases in Traditional Chinese Medicine since decades. In recent studies, shikonin revealed remarkable anticancer activities and thereby is a promising candidate for cancer chemotherapy. However, the underlying cellular mechanisms and targets of shikonin are still unknown. Here, we showed that shikonin indeed exhibits strong cytotoxic effects on a panel of 15 different cancer cell lines also containing multi-drug resistant cells. The strongest effects were obtained on U937 leukemia cells. To better understand the underlying mechanisms, we performed a whole genome expression analysis of these cells after shikonin treatment. Thereby novel molecular key players and genetic networks responsible for the effects of shikonin were identified. Induction of cell cycle arrest, apoptosis and increased levels of reactive oxygen species and DNA damage were revealed as striking cellular effects of shikonin. Furthermore, whole sets of genes responsible for cytoskeletal formation and mitochondrial energy metabolism were deregulated after shikonin treatment. Using cell based assays we showed that shikonin indeed induces G1/S phase cell cycle arrest and caspase 3/7 dependent apoptosis. Furthermore we confirmed the induction of reactive oxygen species and quantified the subsequent DNA damage. In addition shikonin significantly prevents cancer cell migration and cytoskeleton formation by inhibiting the dynamics of the microtubule system. The reason for all this secondary effects was revealed by real-time kinetic uptake experiments based on the intrinsic fluorescence of shikonin. Thereby a rapid cellular uptake and a direct accumulation of the drug in the mitochondria were observed. This caused a breakdown of the mitochondrial membrane potential within the same time range of drug uptake, resulting in a failure of the respiratory chain and the cellular energy production. As the mitochondrial structure and metabolism differs strongly between cancer and normal cells, targeting of mitochondria is a very recent and promising approach in cancer therapy. Our results showed that mitochondria are the primary targets of shikonin in cancer cells and thus we believe that shikonin has the potential in future clinical application.</jats:p> <jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4662. doi:1538-7445.AM2012-4662</jats:p>
Autoren
DOI
10.1158/1538-7445.am2012-4662
eISSN
1538-7445
ISSN
0008-5472
Ausgabe der Veröffentlichung
8_Supplement
Zeitschrift
Cancer Research
Paginierung
4662 - 4662
Datum der Veröffentlichung
2012
Status
Published
Herausgeber
American Association for Cancer Research (AACR)
Herausgeber URL
http://dx.doi.org/10.1158/1538-7445.am2012-4662
Datum der Datenerfassung
2022
Titel
Abstract 4662: Shikonin causes cancer cell death by inducing mitochondrial dysfunction
Ausgabe der Zeitschrift
72

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