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

作者：Alcantara Flores Ela; Enriqueta Brechu Franco Alicia; Garcia Lopez Patricia; Rocha Zavaleta Leticia; Lopez Marure Rebeca; Martinez Vazquez Mariano^*

来源：Molecules, 2015, 20(12): 21125-21137.

DOI：10.3390/molecules201219757

• argentatin B
• colon cancer
• prostate cancer
• cell senescence
• xenografts

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--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--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.

• 出版日期2015-12