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.
Highlights
It is known that natural compounds have been an important source of several clinically useful anti-cancer agents
When tested for senescence associated-β-galactosidase activity,3a proportion of 43% HCT-15, and 66% PC-3 cells showed a positive staining, compared with 2% of untreated controls. These findings suggest that argentatin B inhibits cell proliferation by inducing senescence
The level of p27 was not changed in HCT-15 after 24–48 h argentatin B treatment, and a reduction of p27 expression was observed at 72 h of treatment. These results indicate that treatment with argentatin B induces the cells to undergo senescence
Summary
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