Original Paper Pharmacology	Planta Med 2008; 74: 1701-1708 DOI: 10.1055/s-0028-1088316
© Georg Thieme Verlag KG Stuttgart · New York
Effects of Leuzea carthamoides on Human Breast Adenocarcinoma MCF-7 Cells Determined by Gene Expression Profiling and Functional Assays
Friedemann Gaube1, Stefan Wölfl2, Larissa Pusch3, Ulrike Werner1, Torsten C. Kroll3, Dieter Schrenk4, Rolf W. Hartmann5, Matthias Hamburger6
1 Institute of Pharmacy, University of Jena, Jena, Germany 2 Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany 3 Clinic of Internal Medicine II, University of Jena, Jena, Germany 4 Department of Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany 5 Department of Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Germany 6 Department of Pharmaceutical Sciences, Institute of Pharmaceutical Biology, University of Basel, Basel, Switzerland; formerly Institute of Pharmacy, University of Jena, Jena, Germany

Abstract

Products derived from roots of Leuzea carthamoides (Maral root) are being promoted as dietary supplements with anti-aging, adaptogenic and anabolic activity, without much scientific evidence. We investigated the effects of a lipophilic Leuzea root extract and the major phytoecdysteroid, 20-hydroxyecdysone, in human breast adenocarcinoma MCF-7 cells. Cell proliferation was inhibited by the extract (IC₅₀ = 30 μg/mL) but not by 20-hydroxyecdysone. Genome-wide expression profiling using Affymetrix HG U133 Plus 2.0 microarrays was carried out to analyse effects at the transcriptional level. 241 genes appeared to be differentially expressed after Leuzea treatment, more than after treatment with either 17β-estradiol or tamoxifen. Transcripts linked to cell cycle regulation and DNA replication were highly over-represented and regulated in an anti-proliferative manner. Genes involved in apoptosis were regulated in a pro-apoptotic manner. Expression levels of several oxidoreductase transcripts were strongly induced, most prominent CYP1A1, known to be regulated via the aryl hydrocarbon receptor pathway. An XRE-dependent reporter gene assay confirmed the AhR-agonistic activity of the Leuzea root extract, whereas 20-hydroxyecdysone was not active. Leuzea extract also inhibited 5α-reductase, type II. While the extract significantly modulates cellular activities, the phytoecdysteroids, are most likely not the active principles of L. carthamoides.

Abbreviations

AhR:aryl hydrocarbon receptor

AKR:aldo-keto reductase

CYP1A1:cytochrome P450, family 1, subfamily A, polypeptide 1

E2:17β-estratiol

ER:estrogen receptor

20-HE:20-hydroxyecdysone

Key words

Leuzea carthamoides - Asteraceae - phytoecdysteroids - expression profiling - CYP1A1 - aryl hydrocarbon receptor