Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins.

Abstract

Artemisinin (ARS) and its derivatives are used for the second-line therapy of malaria infections with Plasmodium falciparum and P. vivax. ARSs also reveal profound antitumor activity in vitro and in vivo. In the present investigation, we correlated the mRNA expression data of 89 angiogenesis-related genes obtained by microarray hybridization from the database of the US National Cancer Institute with the 50% growth inhibition concentration values for eight ARSs (ARS, arteether (ARE), artesunate (ART), artemisetene, arteanuine B, dihydroartemisinylester stereoisomers 1 and 2). The constitutive expression of 30 genes correlated significantly with the cellular response to ARSs. By means of hierarchical cluster analysis and cluster image mapping expression, profiles were identified that determined significantly the cellular response to ART, ARE, artemether and dihydroartemisinylester stereoisomer 1. We have exemplarily validated the microarray data of six out of these 30 genes by real-time RT-PCR in seven cell lines. The fact that sensitivity and resistance of tumor cells could be predicted by the mRNA expression of angiogenesis-related genes indicate that ARSs reveal their antitumor effects at least in part by inhibition of tumor angiogenesis. As many chemopreventive drugs exert antiangiogenic features, ARSs might also be chemopreventive in addition to their cytotoxic effects.

• Authors: L Anfosso, T Efferth, A Albini, U Pfeffer
• Journal: The pharmacogenomics journal (Pharmacogenomics J) 2006 Jul-Aug Vol. 6 Issue 4 Pg. 269-78 ISSN: 1470-269X [Print] United States
• PMID: 16432535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenic Proteins
• Antineoplastic Agents
• Artemisinins
• RNA, Messenger

Topics

• Angiogenic Proteins (genetics, metabolism)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Artemisinins (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cluster Analysis
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Humans
• Inhibitory Concentration 50
• Neoplasms (blood supply, drug therapy, metabolism)
• Neovascularization, Pathologic (prevention & control)
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger (metabolism)
• Reproducibility of Results
• Reverse Transcriptase Polymerase Chain Reaction