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

Molecules

Ela Alcántara-Flores²  Alicia Enriqueta Brechú-Franco³  Patricia Garc໚-López⁴  Leticia Rocha-Zavaleta¹  Rebeca López-Marure⁵  Mariano Martínez-Vázquez² 

[1]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

[2]Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, C.P. 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 Nacional de Cardiología “Ignacio Chávez”, Departamento de Biología Celular, Juan Badiano No. 1, Colonia Sección 16, Tlalpan, C.P. 14080, México D.F., Mexico

关键词: argentatin B;    colon cancer;    prostate cancer;    cell senescence;    xenografts;   

DOI  :  10.3390/molecules201219757

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.