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Research Articles: Therapeutics, Targets, and Development

Phytochemistry and pharmacogenomics of natural products derived from traditional chinese medicine and chinese materia medica with activity against tumor cells

¹ German Cancer Research Centre, Pharmaceutical Biology, Heidelberg, Germany; ² Institute of Pharmaceutical Sciences, University of Graz; ³ Joanneum Research, Graz, Austria; ⁴ Institute of Pharmaceutical Biology, University of Düsseldorf, Düsseldorf, Germany; ⁵ Institute of Toxicology, University of Mainz, Mainz, Germany; and ⁶ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China

Requests for reprints: Thomas Efferth, German Cancer Research Centre, Pharmaceutical Biology (C015), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Phone: 49-6221-423426; Fax: 49-6221-423433. E-mail: t.efferth{at}dkfz.de

Abstract

The cure from cancer is still not a reality for all patients, which is mainly due to the limitations of chemotherapy (e.g., drug resistance and toxicity). Apart from the high-throughput screening of synthetic chemical libraries, natural products represent attractive alternatives for drug development. We have done a systematic bioactivity-based screening of natural products derived from medicinal plants used in traditional Chinese medicine. Plant extracts with growth-inhibitory activity against tumor cells have been fractionated by chromatographic techniques. We have isolated the bioactive compounds and elucidated the chemical structures by nuclear magnetic resonance and mass spectrometry. By this strategy, we identified 25-O-acetyl-23,24-dihydro-cucurbitacin F as a cytotoxic constituent of Quisqualis indica. Another promising compound identified by this approach was miltirone from Salvia miltiorrhiza. The IC₅₀ values for miltirone of 60 National Cancer Institute cell lines were associated with the microarray-based expression of 9,706 genes. By COMPARE and hierarchical cluster analyses, candidate genes were identified, which significantly predicted sensitivity or resistance of cell lines to miltirone. [Mol Cancer Ther 2008;7(1):152–61]

Grant support: Joanneum Research, Graz, Austria (S. Kahl).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁷ http://dtp.nci.nih.gov

⁸ http://www.chinese.botanicals.at

Received 1/31/07; revised 9/21/07; accepted 12/ 4/07.