Effects of Leuzea carthamoides DC. on human breast cancer MCF-7 cells detected by gene expression profiling

Products derived from roots of Leuzea carthamoides DC. (Maral root) are being promoted as anti-aging and adaptogenic. The phytoecdysteroids are considered as active principles with numerous beneficial effects [1], but little is known about the pharmacological properties of Leuzea extracts. We, therefore, investigated the effects of a lipophilic Leuzea root extract on the human breast cancer cell line MCF-7. Cell proliferation was inhibited by the extract (IC₅₀=28µg/mL) but not by the major phytoecdysteroid, 20-hydroxyecdysone. Genome-wide expression profiling using Affymetrix HG U133 Plus 2.0 microarrays was carried out to analyze effects at the mRNA level. 241 genes appeared to be significantly regulated. Transcripts of gene products involved with cell cycle progression and DNA replication were decreased, while mRNAs coding for inhibitory products were increased. This was in agreement with the antiproliferative activity of the extract. Upregulation of several pro-apoptotic genes provide evidence that the extract may sensitize the cells for apoptotic events. Downregulation of estrogen receptor α could be confirmed by real-time RT-PCR and Western blot. Additionally, expression levels of several transcripts of enzymes with oxidoreductase activity were induced, including a strong increase of CYP1A1 transcript which is known to be regulated via the aryl hydrocarbon receptor (AhR). AhR-agonistic activity of the Leuzea root extract, but not 20-hydroxyecdysone was confirmed by a XRE-dependent reporter gene assay. This suggests that at least a part of the effects could be due to AhR activation. However, the phytoecdysteroids are not active principles in Leuzea root.

Reference: 1. Sláma, K., Lafont, R. (1995), Eur. J. Entomol. 92: 355–377.