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

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 12; pp. 21125 - 21137
• Main Authors: Alcántara-Flores, Ela, Brechú-Franco, Alicia Enriqueta, García-López, Patricia, Rocha-Zavaleta, Leticia, López-Marure, Rebeca, Martínez-Vázquez, Mariano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-11-2015; MDPI
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; argentatin B; Biotechnology; Blotting, Western; Cadmium; Cell cycle; Cell Cycle - drug effects; Cell growth; Cell proliferation; Cell Proliferation - drug effects; cell senescence; Cellular Senescence - drug effects; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Cyclin-dependent kinase inhibitor p21; Flow Cytometry; Galactosidase; Humans; Lymphocytes B; Male; Mice; Mice, Nude; Proliferating cell nuclear antigen; Prostate; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteins; Senescence; Staining; Toxicity; Triterpenes - pharmacology; Tumor Cells, Cultured; Tumors; Western blotting; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; β-Galactosidase; prostate cancer; xenografts; colon cancer; argentatin B; cell senescence
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules201219757

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.