Effect of chemopreventive agents on differentiation of mouse embryonic stem cells.
Chemopreventive agents are derived from edible plants and from ancient time is a part of daily intake for many humans and animals. There are several lines of compelling evidence from epidemiological, clinical and laboratory studies that these dietary constituents are associated in reducing cancer risks. However, developmental toxicity of these natural compounds cannot be excluded. In the present study, we examined the effect of chemopreventive agents on the differentiation of mouse embryonic stem cells (ESCs) as an in vitro embryotoxicity model. We assumed that inhibition of developmentally regulated genes in vitro might predict developmental toxicity also under in vivo conditions. We found that epigallocatechin gallate (EGCG) (20 microM) induced the expression of mesodermal and cardiomyocyte genes and a significant increase in the number and the percentage of cardiomyocytes. The increase of the subpopulation correlated with higher numbers of beating foci and beating frequencies. Curcumin on the other hand at 0.4 mM was seen to enhance expression of ectodermal transcripts. Quercetin (2.5 microM) was found to inhibit several developmentally regulated genes.
Center of Physiology and Pathophysiology, Institute of Neurophysiology, Robert-Koch Str. 39, 50931 Cologne, Germany.
Vilas
V
Wagh
Smita
S
Jagtap
Kesavan
K
Meganathan
Shiva Prasad
SP
Potta
Johannes
J
Winkler
Juergen
J
Hescheler
Agapios
A
Sachinidis
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D017931:DNA Primers; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D017931:DNA Primers