Effects ofLeuzea carthamoideson Human Breast Adenocarcinoma MCF-7 Cells Determined by Gene Expression Profiling and Functional Assays

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 microg/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 17beta-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 5alpha-reductase, type II. While the extract significantly modulates cellular activities, the phytoecdysteroids, are most likely not the active principles of L. carthamoides.

Effects of 20-hydroxyecdysone, Leuzea carthamoides extracts, dexamethasone and their combinations on the NF-κB activation in HeLa cells

“…Based on Leuzea's traditional use, scientific evidence has been built up since the beginning of the 1960s in the Soviet Union, followed in the 1980s by Eastern European countries, before subsequently attracting interest worldwide [9–11] . As a result, a variety of effects have been described for L. carthamoides , including anabolic, [12,13] cytotoxic, anticancerogenic, antimetastatic, [14,15] tonic/adaptogenic [16–18] and immunomodulating properties [19,20] . Its medicinal applications have been superseded in favour of its use as anabolic ‘functional’ fodder and dietary supplement.…”

The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review

“…A lipophilic Leuzea root extract containing the major PE 20-HE demonstrated potent cytotoxic effects on MCF-7 cells. The extract exhibitied cell proliferation with IC 50 30 μg/mL, yet 20-HE alone was not as effective 171 . Genome-wide expression analysis for differential transcriptional expression of 241 genes showed that Leuzea extract treatment was comparatively more effective that treatment with tamoxifen, a commonly used medication for preventing breast cancer in women 171 .…”

“…The extract exhibitied cell proliferation with IC 50 30 μg/mL, yet 20-HE alone was not as effective 171 . Genome-wide expression analysis for differential transcriptional expression of 241 genes showed that Leuzea extract treatment was comparatively more effective that treatment with tamoxifen, a commonly used medication for preventing breast cancer in women 171 . The cytotoxic potentials of n -butanolic fraction of Ajuga chamaecistus , which mainly contains melilotoside, phenylethyl glycosides, and PEs, were assessed against human cancer cell lines (T47D, HT-29, and Caco-2) and the normal cell line (NIH 3T3) showed no cytotoxicity even up to 400 μg/mL concentration of the extract 172 .…”

Residues at the Indole‐NH of LE300 Modulate Affinities and Selectivities for Dopamine Receptors

“…Moreover, it was of interest to study the effect of the different substituents on the cytotoxicity of the compounds. This was tested in an MTT cell proliferation assay, the protocol has been described 11. (Cc 50 ‐values are given in Table 1).…”