Microarray-based prediction of cytotoxicity of tumor cells to cantharidin.
Cantharidin (CAN) is the active principle of the Chinese blister beetle (Mylabris phalerata) which exerts profound cytotoxicity towards tumor cells. The aim of this study was to identify the molecular determinants of sensitivity and resistance of tumor cells to CAN. We mined the microarray database of the National Cancer Institute (NCI), for genes whose expression correlated with the IC(50) values for CAN of 60 cell lines of different tumor types. By COMPARE analysis Kendall's tau test, and false discovery rate (FDR) analysis, 21 out of 9706 genes or expressed sequence tags (ESTs) were identified. If the mRNA expression of the 21 genes or ESTs was subjected to hierarchical cluster analysis and cluster image mapping, sensitivity or resistance of the 60 cell lines to CAN was predictable with statistical significance. The majority of these genes are involved in DNA damage response, DNA repair, and/or apoptosis. In conclusion, sensitivity or resistance of tumor cells to CAN is multi-factorial in nature. DNA repair and apoptosis play a major role as determinants of cellular response to CAN. The present investigation represents a starting point to dissect the genes and molecular pathways responsible for cellular response to cantharidin in more detail.
Efferth
Thomas
T
German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. thomas.efferth@web.de
D017209:Apoptosis; D002193:Cantharidin / Q000494:pharmacology* / Q000633:toxicity; D016000:Cluster Analysis; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D002193:Cantharidin