Anti-proliferation And Anti-migration Effects Of Chalcone Derivative On Human Neuroblastoma Cells

BACKGROUND & OBJECTIVE: Neuroblastoma is the 4th leading cancer in Children, second only to leukemia, brain tumor and malignant lymphoma, which accounts for 8% to 10% of all children malignancy. So far, no effective treatments has been developed. In the present study, a large number of chalcone derivatives, filtering a derivative, have been scanned for their antiproliferation effects on human neoblastoma cell lines. C37 has been shown the lowest IC50 to SH-SY5 Y cell lines. Then, we study the mechanism of proliferation inhibition and migration behavior in SH-SY5 Y cells when treated with C37.METHODS: The antiproliferation effects of chalcone derivative C37 on tumor cells, especially for SH-SY5 Y cells were detected by CCK-8 assay. Cell cycle distributions and cellular apoptosis in SH-SY5 Y cells were measured by flow cytometry. The expression of apoptosis proteins in SH-SY5 Y cells treated with C37 was detected by Western blot. In addition, we studied the effects of migration inhibition of C37 in SH-SY5 Y cells by wound healing assay and the effects of proteins involved in migration in SH-SY5 Y cells treated by Western blot.RESULTS: When different tumor cell lines were treated with various kinds of synthetic chalcone derivatives for 48 h, we found C37 possessed the best activity in SH-SY5 Y cells, whose median inhibitory concentration(IC50) was 1.42μmol·L-1. We further specifically studied the effects of proliferation inhibition of C37 in SH-SY5 Y cells, finding C37 resulted in various degree inhibition of SH-SY5 Y cells in a dose- and time-dependent manner within certain range. After treating with different concentrations of C37 for 24 h, the percentage of the total SH-SY5 Y cells at the G1 phase increased while the S phase dropped accordingly. The results shown that the cell cycle of SH-SY5 Y cells was blocked in G1 phase. Moreover, with the increase of concentration of C37, the apoptosis rate of SH-SY5 Y cells was ever-increasing, which shown that C37 could induce apoptosis of SH-SY5 Y cells. Western blot results shown that the expression quantity of anti-apoptosis proteins Bcl-2 decreased gradually andpro-apoptotic proteins, Bax, p-p38, caspase-3, caspase-9 and p53, rose in a dose-dependent manner with the increase of concentration of C37, which were consistent with flow cytometry results. The results of wound healing assay shown that the migration significantly decreased when treated with C37. Western blot results shown that the expression of MMP-2 and MMP-9 decreased progressively when treated with C37, which shown that C37 regulates the migration of SH-SY5 Y cells by decreasing the expression of matrix metalloproteinases.CONCLUSION: C37 can inhibit the proliferation of SH-SY5 Y cells by inducing cell apoptosis of SH-SY5 Y cells and the molecular mechanisms involving the apoptosis-related proteins such as Bcl-2, Bax, caspase-3, caspase-9, p53 and Erk. In addition, C37 reduced the migration of SH-SY5 Y cells by lowering the expression of matrix metalloproteinases such as MMP-2 and MMP-9.