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Tautomycetin induces apoptosis of human breast cancer cell line MCF-7/ADR and its mechanism
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Abstract:
Objective：To investigate the effects of tautomycetin on the proliferation and apoptosis of human breast cancer cell line MCF-7/ADR and the related mechanism. Methods: The effect of tautomycetin on the proliferation of MCF-7/ADR cells was examined by MTT assay; its effect on apoptosis of MCF-7/ADR cells was assessed by flow cytometry; and its effects on expressions of caspase-related proteins, Bcl-2, cytochrome C (Cyto-C), P53 and Akt in MCF-7/ADR cells were detected by Western blotting. Results: Tautomycetin inhibited the proliferation of MCF-7/ADR cells in a dose-dependent manner （0.01~100 μmol/L，P<0.05), with the IC50 value of (1.26±0.12) μmol/L. Compared with the control group, the early apoptosis rate of MCF-7/ADR cells after 1 μmol/L tautomycetin treatment was increased from (0.67±0.18)% to (17.2±3.8)%, and the late apoptosis rate from (0.96±0.23)% to (28.4±5.7)%, (P<005); tautomycetin activated caspase-9 and caspase-7, decreased Bcl-2 expression, promoted Cyto-C secretion and decreased p-Akt levels in MCF-7/ADR cells, while showed no obvious effect on caspase-8 and P53 expressions. Conclusion: Tautomycetin can inhibit the phosphorylation of Akt, and induce the Cyto-C-mediated apoptosis of MCF-7/ADR cells in a P53-independent pathway.
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Project supported by the National Foundation for Distinguished Young Scientists of China (No.30688003)
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