Bufalin combined with hydroxycamptothecin affect in vitro cell growth and apoptosis of human Du 145 prostate cancer cells

Objectives: To investigate the effect of different bufalin doses combined with 7-ethyl-10-hydroxy-camptothecin (HCPT) on the growth and apoptosis of human Du145 prostate cancer cells in vitro and analyze related mechanisms. Methods: We investigated the inhibiting effect of single, sequential or combined use of different bufalin and HCPT doses on human prostate cancer cells Du145 via flow cytometry and cell viability assays and determined caspase 3 and 9 expression. Results: The growth rates of Du145 cells were significantly reduced by single applications of bufalin and HCPT in dose and time dependent manners. Bufalin arrested the Du145 cells in the G2/M whereas HCPT in the S phase. Combined simultaneous application of bufalin and HCPT led to antagonistic effects with reduced growth inhibitions, whereas combined sequential application led to synergistic effects with highest proliferation reduction, particularly with initial HCPT followed by bufalin exposure of the cells. The expression of caspase 3 and 9 was upregulated after single use of HCPT and bufalin and further upregulated after sequential use. Conclusions: Sequential use of bufalin after HCPT exposure led to the highest synergistic growth inhibition effects on Du145 cells, which might be attributed to the ability of the drugs to block cell cycles in both G2/M and S phases and upregulation of casapase-3 and caspase 9 apoptosis factor expressions.