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Molecules 2015, 20(12), 21125-21137; doi:10.3390/molecules201219757

Argentatin B Inhibits Proliferation of Prostate and Colon Cancer Cells by Inducing Cell Senescence

1
Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, C.P. 04510, México D.F., Mexico
2
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad Universitaria 3000, Coyoacán, CP. 04510, México D.F., Mexico
3
Facultad de Ciencias, Departamento de Ecología y Recursos Naturales, Universidad Nacional Autónoma de México, Coyoacán, C.P. 04510, México D.F., Mexico
4
Instituto Nacional de Cancerología, Subdirección de Investigación Básica, Tlalpan, C.P. 14080, México D.F., Mexico
5
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
6
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
*
Author to whom correspondence should be addressed.
Academic Editor: Isabel C. F. R. Ferreira
Received: 2 September 2015 / Revised: 13 November 2015 / Accepted: 17 November 2015 / Published: 27 November 2015
(This article belongs to the Collection Bioactive Compounds)
View Full-Text   |   Download PDF [2769 KB, uploaded 27 November 2015]   |  

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. View Full-Text
Keywords: argentatin B; colon cancer; prostate cancer; cell senescence; xenografts argentatin B; colon cancer; prostate cancer; cell senescence; xenografts
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Alcántara-Flores, E.; Brechú-Franco, A.E.; García-López, P.; Rocha-Zavaleta, L.; López-Marure, R.; Martínez-Vázquez, M. Argentatin B Inhibits Proliferation of Prostate and Colon Cancer Cells by Inducing Cell Senescence. Molecules 2015, 20, 21125-21137.

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