Antiproliferation Effects Of Petasin And Chalcone On Human Neuroblastoma Cells

BACKGROUND&OBJECTIVE:Neuroblastoma is an embryonal malignancy of postganglionic sympathetic nervous system, one of the most common extracranial solid tumors in children. There is high morbidity and mortality of the tumor in infants and young children, with poor prognosis. So far, there is no effective way to improve this situation. We studied the effects of petasin and two novel compounds of chalcones on anti-human neuroblastoma and its mechanism, and provided preliminary experimental evidence for petasin and two novel compounds of chalcones using on the prevention and treatment of neuroblastoma.METHODS:The antiproliferation effects of the compounds on tumor cells were detected by SRB assay. Cell cycle distributions were measured by flow cytometry. Cellular apoptosis was detected by Hoechst33258staining assay and flow cytometry. The growth of SK-N-SH and SH-SY5Y cells were established by cell counting, and the proliferation of SK-N-SH and SH-SY5Y cells following removal of petasin were established by the same method. Cell senescence of SK-N-SH was observed by β-galactosidase staining assay. The phosphorylation of ERK1/2and MEK of SK-N-SH was determined by western blot. The positive control of experiment is cisplatin.RESULTS:Petasin resulted in various degree inhibition of SK-N-SH, SH-SY5Y, SK-N-BE(2), SGC7901, SMMC7721, EC9706, and U251cells in a dose-and time-dependent manner within certain range. After treated with petasin, the cell cycle of SK-N-SH arrested in G1phase, and there was no apoptosis shown neither by Hoechst33258staining nor flow cytometry analysis. And petasin did not induce SK-N-SH cells senescence. The capacity of proliferation and cell cycle of SK-N-SH following removal of petasin had returned to normal levels. In correspond, there was apoptosis shown both by Hoechst33258staining and flow cytometry analysis in SH-SY5Y after treated with petasin. And the proliferation capacity of SH-SY5Y following removal of petasin had not returned to normal levels. In the end, western blot analysis observed that the phosphorylation of ERK1/2and MEK was decreased by pretreatment with petasin in transiently. At the same times, compound A and B resulted in various degree inhibitions of SK-N-SH cells in a dose-and time-dependent manner within certain range. After treated with compound A and B, the cell cycle of SK-N-SH were arrested in G1and G2M phase, respectively. And there was apoptosis shown both by Hoechst33258staining and flow cytometry analysis.CONCLUSION:Petasin can inhibit the proliferation of SK-N-SH and SH-SY5Y. Petasin-treated SK-N-SH cells just were inhibited the cell proliferation, the mechanism may be associated with down-regulation the phosphorylation of ERK1/2and MEK protein. Novel compounds of chalcones can inhibit the proliferation of SK-N-SH, and the mechanism may be related with changing cell cycle distribution and inducing apoptosis.