title: Genipa americana (Rubiaceae) fruit extract affects mitogen-activated protein kinase cell pathways in human trophoblast-derived BeWo cells: implications for placental development.
abstract: Genipa americana L. (Rubiaceae) is a fruit tree and a traditional medicine used to treat anemia, icterus, asthma, and liver and spleen problems. The aim of the present study was to verify the effect of G. americana fruit ethanolic extract on the mechanism for proliferation and differentiation of trophoblast-like cells. Qualitative analysis of G. americana fruit extract was performed, and BeWo cells, a well-established placental choriocarcinoma cell line that can undergo differentiation, were used to analyze cell viability and proliferation. Methods consisted of cytotoxic and proliferation measurement, detection of release of human chorionic gonadotrophins, cell fusion observation, and evaluation of cell-signaling pathways (production of cyclic adenosine monophosphate and phosphorylation of mitogen-activated protein kinases [MAPKs]). A stock solution of the extract was diluted in Ham's F-12 medium with 10% fetal bovine serum at concentrations ranging from 50 to 1000 μg/mL. Cells treated with dimethylsulfoxide, forskoline, and MAPK inhibitors (PD98059 or SB203580) were used as a control. Forskoline was used to induce the differentiation state in BeWo cells. Phytoanalysis indicated the presence of steroids only. Results showed that the G. americana fruit extract did not cause any cytotoxicity or interference in cell differentiation. However, a significant antiproliferative state related to inhibition and reactivation of ERK1/2 and p38 MAPK in BeWo cells was seen. These results suggest that steroids from G. americana may affect placental cell regulation.
authors.affiliation: Laboratory of Maternal-Fetal Physiology, Department of Biological Sciences, University of Quebec at Montreal, Montreal, Quebec, Canada.
authors.forename: Aline Oliveira
authors.initials: AO
authors.lastname: da Conceição
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Rossi
authors.forename: Fernando Faustino
authors.initials: FF
authors.lastname: de Oliveira
authors.forename: Larissa
authors.initials: L
authors.lastname: Takser
authors.forename: Julie
authors.initials: J
authors.lastname: Lafond
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004341:Drug Evaluation; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010929:Placentation / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D019666:Rubiaceae / Q000737:chemistry*; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D005419:Flavonoids; D007093:Imidazoles; D010936:Plant Extracts; D011725:Pyridines; D000249:Adenosine Monophosphate; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004121:Dimethyl Sulfoxide