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Cytotoxic activity and chemical composition of the root extract from the mexican species Linum scabrellum: mechanism of action of the active compound 6-Methoxypodophyllotoxin

AutorAlejandre-García, Ivonne; Álvarez, Laura ; Cardoso-Taketa, Alexandre; González-Maya, Leticia; Antúnez, Mayra; Salas-Vidal, Enrique; Díaz, José Fernando ; Marquina-Bahena, Silvia; Villarreal, María Luisa
Fecha de publicación2015
EditorHindawi Publishing Corporation
CitaciónEvid Based Complement Alternat Med.: :298463 (2015)
ResumenThe cytotoxic activity and the chemical composition of the dichloromethane/methanol root extract of Linum scabrellum Planchon (Linaceae) were analyzed. Using NMR spectra and mass spectrometry analyses of the extract we identified eight main constituents: oleic acid (1), octadecenoic acid (2), stigmasterol (3), α-amyrin (4), pinoresinol (5), 6 methoxypodophyllotoxin (6), coniferin (7), and 6-methoxypodophyllotoxin-7-O-β-D-glucopyranoside (8). By using the sulforhodamine B assay, an important cytotoxic activity against four human cancer cell lines, HF6 colon (IC50 = 0.57 μg/mL), MCF7 breast (IC50 = 0.56 μg/mL), PC3 prostate (IC50 = 1.60 μg/mL), and SiHa cervical (IC50 = 1.54 μg/mL), as well as toward the normal fibroblasts line HFS-30 IC50 = 1.02 μg/mL was demonstrated. Compound 6 (6-methoxypodophyllotoxin) was responsible for the cytotoxic activity exhibiting an IC50 value range of 0.0632 to 2.7433 µg/mL against the tested cell lines. Cell cycle studies with compound 6 exhibited a cell arrest in G2/M of the prostate PC3 cancer cell line. Microtubule disruption studies demonstrated that compound 6 inhibited the polymerization of tubulin through its binding to the colchicine site (binding constant K b = 7.6 × 10(6) M(-1)). A dose-response apoptotic effect was also observed. This work constitutes the first investigation reporting the chemical composition of L. scabrellum and the first study determining the mechanism of action of compound 6.
Descripción12 p.-6 fig.-1 tab.
Versión del editorhttp://dx.doi.org/10.1155/2015/298463
URIhttp://hdl.handle.net/10261/121341
DOI10.1155/2015/298463
ISSN1741-427X
E-ISSN1741-4288
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