shikonin directly targets mitochondria and causes mitochondrial dysfunction in cancer cells紫草素直接目标线粒体和导致癌症细胞线粒体功能障碍.pdfVIP

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 726025, 15 pages doi:10.1155/2012/726025 Research Article Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells Benjamin Wiench,1 Tolga Eichhorn,1 Malte Paulsen,2 and Thomas Efferth1 1 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany 2 Cytometry Core Facility, Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany Correspondence should be addressed to Thomas Efferth, efferth@uni-mainz.de Received 10 July 2012; Accepted 7 September 2012 Academic Editor: Ke Liu Copyright © 2012 Benjamin Wiench et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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