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免疫病理疾病及治疗学论文学
SJR: 0.309 SNIP: 0.041 CiteScore™: 0.18

ISSN 打印: 2151-8017
ISSN 在线: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

免疫病理疾病及治疗学论文学

DOI: 10.1615/ForumImmunDisTher.2012004452
pages 315-322

Microarray-Based Determination of Response of Tumor Cells to Cycloshikonin

Thomas Efferth
Department of Pharmaceutical Biology Institute of Pharmacy and Biochemistry Johannes Gutenberg University, Mainz, Germany
Henry Johannes Greten
Heidelberg School of Traditional Chinese Medicine, Heidelberg, Germany and Biomedical Sciences Institute Abel Salazar, University of Porto, Portugal

ABSTRACT

Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with various biological activities. Cycloshikonin is a metabolite, which appears during biotransformation of shikonin in the gastrointestinal tract. We performed a COMPARE analysis with >1400 standard antitumor agents included in the NCI database to identify drugs whose IC50 values correlate with those of cycloshikonin. Drugs with the highest correlation coefficients were either antimetabolites (e.g., caracemide, rifamycin, diglycoaldehye, asalex) or DNA-damaging alkylating agents (e.g., pibenzimol dihydrochloride, pyrimidine-5-glycodialdehyde). Although the major target of antimetabolic compounds is the inhibition of nucleic acid biosynthesis, many antimetabolites are also known to induce DNA damage. It is, therefore, reasonable to speculate that cycloshikonin might also damage DNA. Next, we performed correlation-based COMPARE analysis of the IC50 values for cycloshikonin and the microarray-based transcriptome-wide mRNA expression of the cell line panel. Among the genes that were associated with cellular response to cycloshikonin were genes from diverse functional groups such as transcription factors and signal transduction (RXF5, ZNF142, POLR3C, NUDT3, CXCR5), structural components of ribosomes (RPS15A, RLP17, RPL30, RPS27, RPS10, RPL5, RPL6, RPL32, RPL41), oxidative stress response and oxidoreductases (RDH14, GCLM, TXNRD1, SRXN1, EPHX1), cytoskeletal elements (ASPH, KRT83, TXNRD1, CAPNS1) and others (PIGR, PPIP5K2, DNAH1, SNPRE, HPS1, SLC7A11, GPC1, CLPTM1, ADAM9, ATP1B1, ANXA1). This microarray-based investigation delivered novel candidate genes that were associated with the response of cancer cells to cycloshikonin. These results merit further investigation to prove the causative contribution of these genes to resistance and sensitivity toward cycloshikonin.


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