Cytotoxic Activity and Chemical Composition of the Root Extract from the Mexican Species Linum scabrellum: Mechanism of Action of the Active Compound 6-Methoxypodophyllotoxin
Por:
Alejandre-Garcia I., Alvarez L., Cardoso-Taketa A., Gonzalez-Maya L., Antunez M., Salas-Vidal E., Diaz J.F., Marquina-Bahena S., Villarreal M.L.
Publicada:
1 ene 2015
Categoría:
Complementary and Alternative Medicine
Resumen:
The 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), alpha-amyrin (4),
pinoresinol (5), 6 methoxypodophyllotoxin (6), coniferin (7), and
6-methoxypodophyllotoxin-7-O-beta-D-glucopyranoside (8). By using the
sulforhodamine B assay, an important cytotoxic activity against four
human cancer cell lines, HF6 colon (IC50 = 0.57 mu g/mL), MCF7 breast
(IC50 = 0.56 mu g/mL), PC3 prostate (IC50 = 1.60 g/mL), and SiHa
cervical (IC50 = 1.54 mu g/mL), as well as toward the normal fibroblasts
line HFS-30 IC50 = 1.02 mu g/mL was demonstrated. Compound 6
(6-methoxypodophyllotoxin) was responsible for the cytotoxic activity
exhibiting an IC50 value range of 0.0632 to 2.7433 mu g/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 x 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.
Filiaciones:
Alejandre-Garcia I.:
Centro de Investigacion en Biotecnologia, Universidad Autonoma Del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, Cuernavaca, 62209, Mexico
Alvarez L.:
Centro de Investigaciones Quimicas IICBA, Universidad Autonoma Del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, Cuernavaca, 62209, Mexico
Cardoso-Taketa A.:
Centro de Investigacion en Biotecnologia, Universidad Autonoma Del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, Cuernavaca, 62209, Mexico
Gonzalez-Maya L.:
Facultad de Farmacia, Universidad Autonoma Del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, Cuernavaca, 62209, Mexico
Antunez M.:
Centro de Investigaciones Quimicas IICBA, Universidad Autonoma Del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, Cuernavaca, 62209, Mexico
Salas-Vidal E.:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62209, MOR, Mexico
Diaz J.F.:
Centro de Investigaciones Biologicas, Madrid, 28040, Spain
Marquina-Bahena S.:
Centro de Investigaciones Quimicas IICBA, Universidad Autonoma Del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, Cuernavaca, 62209, Mexico
Villarreal M.L.:
Centro de Investigacion en Biotecnologia, Universidad Autonoma Del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, Cuernavaca, 62209, Mexico
All Open Access, Gold
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