Anti-tumor Effect of Piceatannol on Triple Negative Breast Cancer Cell Line MDA-MB-468 and Its Mechanism / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of piceatannol （PIC） on the proliferation， apoptosis and cell cycle of MDA-MB-468 triple negative breast cancer cells and its mechanism. Method:The methylthiazolyldiphenyl-tetrazoliu bromide （MTT） colcorimetry method was used to investigate the effect of different concentrations of PIC （0， 2.5， 5.0， 10.0， 20.0， 40.0， 80.0， 160.0 μmol·L^-1） on the cell viabilities of triple negative breast cancer MDA-MB-468 cells and calculate the half maximal inhibitory concentration （IC₅₀） value， the effect of different concentrations of PIC （5.0， 10.0， 20.0 μmol·L^-1） on the cell cycle of MDA-MB-468 were investigated by flow cytometry with propidium iodide （PI） staining. The apoptotic effect of PIC （5.0， 10.0， 20.0 μmol·L^-1） on MDA-MB-468 cells in triple negative breast cancer was investigated by flow cytometry with cell apoptosis detection Annexin V-FITC and PI double staining. Western blot was used to investigate the effect of different concentrations of PIC （5.0， 10.0， 20.0 μmol·L^-1） on the proliferation and apoptosis of MDA-MB-468 cells and detect the expressions ofsecreted glycoprotein Wnt/<italic>β</italic>-catenin pathway related proteins. Result:MTT results showed that compared with the blank group， PIC could inhibit the proliferation of MDA-MB-468 cells in a concentration-dependent manner （<italic>P</italic><0.05， <italic>P</italic><0.01）， with IC₅₀ at（39.4±4.6）μmol·L^-1. Compared with the blank group， PIC could increase the percentage of MDA-MB-468 cells in G₀/G₁ phase about cell cycle in a concentration-dependent manner （<italic>P</italic><0.01）. Compared with the blank group， 5.0， 10.0， 20.0 μmol·L^-1 PIC could induce apoptosis of MDA-MB-468 cells for 48 h（<italic>P</italic><0.01）， and the apoptosis rate of MDA-MB-468 cells reached 49.87% when treated with 20.0 μmol·L^-1 for 48 h. Compared with the blank group， PIC could significantly reduce the expressions of <italic>β</italic>-catenin， proto-oncogene （C-myc） and adhesion factor （CD44） proteins in MDA-MB-468 cells， significantly inhibit the phosphorylation of<italic> </italic>protein kinase B （Akt） and p38 mitogen activated protein kinase （p38 MAPK） proteins and the protein expression of B lymphocyte tumor-2 （Bcl-2）， and enhance cysteine aspartic acid protease-3 （Caspase-3）， Bcl-2 related X protein （Bax） and phosphorylated <italic>β</italic>-catenin protein expression（<italic>P</italic><0.01）. Conclusion:PIC may inhibit the proliferation of MDA-MB-468 cells by inhibiting the Wnt/<italic>β</italic>-catenin signaling pathway， block the cell cycle in G0/G1 phase， and induce its apoptosis.