Salinomycin reduced viability of prostate cancer cells at a lower dose than nonmalignant prostate epithelial cells

Our recent study has revealed that salinomycin induces apoptosis in human prostate cancer cells by accumulated reactive oxygen species and mitochondrial membrane depolarization [20]. Using androgen-independent PC-3 and DU-145, the androgen-dependent LNCaP prostate cancer cells and non-malignant RWPE-1 prostate epithelial cells, we examined the effects of salinomycin on the viability of prostate cancer cells. When the cells were treated with increasing concentrations of salinomycin for different time periods, the viability of prostate cancer cells were reduced in a dose- and time-dependent manner (Fig. 2A, 2B and 2C). By comparison, RWPE-1 cells were relatively less sensitive to salinomycin, since at 0.15 ||M concentration, the drug did not significantly inhibit viable cell number (Fig. 2D), unlike the all three cancer cells, which showed significant drop in viability in MTT assay. To some extent, differential sensitivity to the drug was also seen for LNCaP vs PC3 and DU-145 cells, since at 1.33 |M of the drug, LNCaP cells manifested a stronger inhibition -- viability reduced to ~55%, 38%, 35% and 22% (after 12 h, 24 h, 36 h and 48 h, respectively), whereas >50% of PC-3 and DU-145 cells remained viable after 36 h treatment of the drug (at 1.33 |M), and even at 48 h, >30% of PC-3 cells and >50% of DU-145 cells remained viable (Fig. 2B vs. Figs 2A & 2C). At 0.15 |M salinomycin, the three cell lines showed approximately similar sensitivity to the drug. To summarize, these results indicate that the chemo-resistance of the hormone-independent cancer cells to salinomycin is higher than that of the hormone-dependent cells, and compared to the cancer cells, non-malignant prostate epithelial cells (such as RWPE-1) are relatively more resistant to salinomycin. We next focused on the PC-3 cell model to investigate the molecular events associated with the salinomycin-induced loss of cell viability [20].

Figure 2. Salinomycin inhibited viability of prostate cancer cells. (A) PC-3 (B) LNCaP (C) DU-145 (D) RWPE-1 cells. 5 x 104 cells/ml were treated with salinomycin (0.15-4.00 ^M) at different time points (12 h, 24 h, 36 h and 48 h). Cell viability was determined by MTT assay. Data are presented as mean ± SD (n = 3 in each group). #p<0.05, p<0.01, *p<0.001 vs. the control group.

Figure 2. Salinomycin inhibited viability of prostate cancer cells. (A) PC-3 (B) LNCaP (C) DU-145 (D) RWPE-1 cells. 5 x 104 cells/ml were treated with salinomycin (0.15-4.00 ^M) at different time points (12 h, 24 h, 36 h and 48 h). Cell viability was determined by MTT assay. Data are presented as mean ± SD (n = 3 in each group). #p<0.05, p<0.01, *p<0.001 vs. the control group.

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