Antiproliferative effect of flavomannin-6,6'-dimethylether from Tricholoma equestre on Caco-2 cells.
Several studies have been performed reporting antitumoral activity of different mushroom extracts. The current study reports the antiproliferative activity of flavomannin-6,6'-dimethylether obtained from a very common edible mushroom: Tricholoma equestre(L.)P.Kumm, and the characterization of its effects at molecular level. Concentrations causing 50% and 80% growth inhibition on human adenocarcinoma colorectal Caco-2 cells were determined (in microg/mL: IC(50)=96+/-3 after 24 h and 78+/-7 after 48 h, IC(80)=112+/-4 after 24 h and 90+/-3 after 48 h) by using MTT method. It was demonstrated that flavomannin-6,6'-dimethylether induced an arrest in G0/G1 phase of the cell cycle by flow cytometry analysis and an increase of p27 protein level by Western blot. Furthermore, this compound did not induce apoptosis by flow cytometry or DNA fragmentation by gel electrophoresis. Thus, it could be a promising agent due to its cytostatic effect against Caco-2 tumoral cells, and the absence of a genotoxic effect.
Pachón-Peña
Gisela
G
Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona (IBUB) and Unit Associated with CSIC, Diagonal 645, Barcelona, Spain. giselapachon@yahoo.com
Reyes-Zurita
Fernando J
FJ
Deffieux
Gerard
G
Azqueta
Amaia
A
de Cerain
Adela López
AL
Centelles
Josep J
JJ
Creppy
Edmond E
EE
Cascante
Marta
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000873:Anthracenes / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D013997:Time Factors; D055439:Tricholoma / Q000737:chemistry*
D000873:Anthracenes; D000970:Antineoplastic Agents; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; C544127:flavomannin-6,6'-dimethylether; D050760:Cyclin-Dependent Kinase Inhibitor p27