Abstract
We previously established a panel of human cancer cell lines, JFCR39, coupled to an anticancer drug activity database; this panel is comparable with the NCI60 panel developed by the National Cancer Institute. The JFCR39 system can be used to predict the molecular targets or evaluate the action mechanisms of the test compounds by comparing their cell growth inhibition profiles (i.e., fingerprints) with those of the standard anticancer drugs using the COMPARE program. In this study, we used this drug activity database-coupled JFCR39 system to evaluate the action mechanisms of various chemical compounds, including toxic chemicals, agricultural chemicals, drugs, and synthetic intermediates. Fingerprints of 130 chemicals were determined and stored in the database. Sixty-nine of 130 chemicals (∼60%) satisfied our criteria for the further analysis and were classified by cluster analysis of the fingerprints of these chemicals and several standard anticancer drugs into the following three clusters: 1) anticancer drugs, 2) chemicals that shared similar action mechanisms (for example, ouabain and digoxin), and 3) chemicals whose action mechanisms were unknown. These results suggested that chemicals belonging to a cluster (i.e., a cluster of toxic chemicals, a cluster of anticancer drugs, etc.) shared similar action mechanism. In summary, the JFCR39 system can classify chemicals based on their fingerprints, even when their action mechanisms are unknown, and it is highly probable that the chemicals within a cluster share common action mechanisms.
Footnotes
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This work was supported in part by Grant-in-Aid 17390032 for Scientific Research (B) from Japan Society for the Promotion of Science (to T.Y.); Ministry of Health, Labor, and Welfare Grants-in-Aid H15-kagaku-002, H16-kagaku-003 (to T.Y. and J.K.); Grant-in-Aid 18015049 of the Priority Area “Cancer” from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to T.Y.); and grant 05-13 from National Institute of Biomedical Innovation Japan (to T.Y.)
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N. N. and T. N. equally contributed to this study.
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
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doi:10.1124/mol.107.038836.
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ABBREVIATIONS: GI50, 50% growth inhibition concentration; GI50, 50% growth inhibition; SN-38, 7-ethyl-10-hydroxycamptothecin; SV-NN, snake venom from N. nigricollis; SV-NNK; snake venom from N. naja kaouthia.
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The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.
- Received June 6, 2007.
- Accepted August 16, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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