Effect of a plant-derived natural compound, Flavin7, on the ERK signaling pathway in immortalized mouse proximal tubule cells.
BACKGROUND
Since MAP kinases represent an important pathway of transducing external stimuli to internal signals in cells, determining their possible role in cancer cells may offer a promising way for the treatment and prognosis of malignant diseases. Our previous experiments have shown that a flavonoid-rich solution, Flavin7, was able to diminish kidney tumor growth in vivo.


METHODS
Effects of Flavin 7 on the MAPK signaling pathway were determined in immortalized mouse proximal tubule cells by determining cell viability, flow cytometric analysis, luciferase assays and Western blots.


RESULTS
At a nontoxic dose, Flavin7 markedly reduced phosphorylation of ERK and inhibited activity of its downstream targets such as Elk1 and CREB via inhibition of the ERK-kinase MEK1.


CONCLUSIONS
Because of its ability to temporarily inhibit kidney tumor growth and activation of the MEK1/ERK pathway in vitro, further in vivo investigations may determine the potential role of Flavin7 in the treatment of malignancies.
Nádasi
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Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veteran HealthCare System, Little Rock, AR 72205, USA. edit.nadasi@aok.pte.hu
Ember
István
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Arany
István
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D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005415:Flavins / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D001688:Biological Products; D005415:Flavins; D010936:Plant Extracts; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases