title: Argentatin B Inhibits Proliferation of Prostate and Colon Cancer Cells by Inducing Cell Senescence.
abstract: Argentatin B has been shown to inhibit the growth of colon HCT-15, and prostate PC-3 cancer cells. However, the mechanism by which argentatin B inhibits cell proliferation is still unknown. We aimed to investigate the mechanism by which argentatin B inhibits cell proliferation. The cell cycle was studied by flow cytometry. Apoptosis was evaluated by Annexin-V-Fluos, and Hoechst 33342 dye staining. Cell senescence was evaluated by proliferation tests, and staining for SA-β-galactosidase. Senescence-related proteins (PCNA, p21, and p27) were analyzed by Western blotting. Potential toxicity of argentatin B was evaluated in CD-1 mice. Its effect on tumor growth was tested in a HCT-15 and PC-3 xenograft model. Argentatin B induced an increment of cells in sub G1, but did not produce apoptosis. Proliferation of both cell lines was inhibited by argentatin B. Forty-three percent HCT-15, and 66% PC-3 cells showed positive SA-β-galactosidase staining. The expression of PCNA was decreased, p21 expression was increased in both cell lines, but p27 expression increased only in PC-3 cells after treatment. Administration of argentatin B to healthy mice did not produce treatment-associated pathologies. However, it restricted the growth of HCT-15 and PC-3 tumors. These results indicate that treatment with argentatin B induces cell senescence.
authors.affiliation: Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, C.P. 04510, México D.F., Mexico. elaalfl@hotmail.com.|Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad Universitaria 3000, Coyoacán, CP. 04510, México D.F., Mexico. elaalfl@hotmail.com.
authors.forename: Ela
authors.initials: E
authors.lastname: Alcántara-Flores
authors.affiliation: Facultad de Ciencias, Departamento de Ecología y Recursos Naturales, Universidad Nacional Autónoma de México, Coyoacán, C.P. 04510, México D.F., Mexico. aliciae@ciencias.unam.mx.
authors.forename: Alicia Enriqueta
authors.initials: AE
authors.lastname: Brechú-Franco
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, Tlalpan, C.P. 14080, México D.F., Mexico. pgarcia_lopez@yahoo.com.mx.
authors.forename: Patricia
authors.initials: P
authors.lastname: García-López
authors.affiliation: Instituto de Investigaciones Biomédicas, Departamento de Biología Molecular y Biotecnología, Universidad Nacional Autónoma de México, Circuito Escolar s/n, Coyoacán, C.P. 04510, México, D.F., Mexico. lrochaz@biomedicas.unam.mx.
authors.forename: Leticia
authors.initials: L
authors.lastname: Rocha-Zavaleta
authors.affiliation: Instituto Nacional de Cardiología "Ignacio Chávez", Departamento de Biología Celular, Juan Badiano No. 1, Colonia Sección 16, Tlalpan, C.P. 14080, México D.F., Mexico. rlmarure@yahoo.com.mx.
authors.forename: Rebeca
authors.initials: R
authors.lastname: López-Marure
authors.affiliation: Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, C.P. 04510, México D.F., Mexico. marvaz@unam.com.
authors.forename: Mariano
authors.initials: M
authors.lastname: Martínez-Vázquez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014315:Triterpenes; C474473:argentatin B
keywords: argentatin B; cell senescence; colon cancer; prostate cancer; xenografts