Lantana macrophylla Schauer (Verbenaceae) ethanolic extract induces activation of ERK1/2 and p38 MAPKs pathway and Ca2+ imbalance in human trophoblasts derived cell lines.
Lantana macrophylla Schauer (Verbenaceae) a medicinal plant used to treat menstrual and respiratory disorders was investigated. The ethanolic extract from leaves was subjected to phytochemical and biological analysis. BeWo and JEG-3 cells were used to evaluate human chorionic gonadotropin hormone (hCG) production, syncytial formation, Ca2+ uptake and Ca2+ handling protein expression. The cAMP production and the mitogen-activated protein kinases (MAPKs) phosphorylation were also investigated. Phytochemical analysis yield three triterpenes: oleanolic, ursolic and latonolic acid. Viability assay showed no significant cytotoxic effect. A significant decrease in hCG production but not a disturbance on BeWo cell fusion were observed. The cAMP pathway was not affected by L. macrophylla extract alone; although the cAMP production inducted by forskolin was diminished. Both ERK1/2 and p38 MAPKs pathways were activated. Increased intracellular Ca2+ concentration ([Ca2+]i) was observed after 24 h treatment in a time and dose dependent manner; however only L. macrophylla at 10 μg/mL induced increased [Ca2+]i after 10 min treatment. CaBP28K and PMCA1/4 were modulated at protein and mRNA levels, respectively. This study showed for the first time the effect of triterpenoids from L. macrophylla leaves on trophoblasts-like cells and indicates a potential toxic effect of this plant in the placental development and fetal growth.
Laboratoire de Physiologie Materno-foetale, Département des Sciences Biologiques, Centre de Recherches Biomédicales, Université du Québec à Montréal, Montréal, Québec, Canada.
Aline O
AO
da Conceição
Fernando F
FF
de Oliveira
Rosilene A
RA
de Oliveira
Ademir
A
de J da S Junior
Larissa
L
Takser
Carlos
C
Reyes-Moreno
Julie
J
Lafond
D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D017931:DNA Primers; D004789:Enzyme Activation; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D032410:Lantana / Q000737:chemistry*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D017931:DNA Primers; D010936:Plant Extracts; D000431:Ethanol; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium