Gene Expression Profiling from a Prostate Cancer PC-3 Cell Line Treated with Salinomycin Predicts Cell Cycle Arrest and Endoplasmic Reticulum Stress

Previously, we reported that salinomycin induces apoptosis of human prostate cancer cells through accumulated reactive oxygen species and mitochondrial membrane depolarization. To extend our understanding for the genomewide expression pattern, we performed cDNA microarray analysis for gene expression profiles in prostate PC-3 cells treated with salinomycin. We found a couple of differences from gene expression profiles. First of them, cyclins and cyclin-dependent kinases were down-regulated, whereas cyclin dependent kinase inhibitors were upregulated, implicating inhibition of cell cycle progression. Second, HSPA5/Bip, DDIT3/CHOP, TRIB3, ATF4 and ATF6 regarding endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were increased at mRNA and protein levels, indicating salinomycin-induced growth inhibition of PC-3 cells seem to be mediated through induction of ER stress and activation of the UPR pathway. Our finding should be useful for understanding genomewide expression patterns of salinomycin-mediated cell cycle arrest and ER stress response toward induction of apoptosis and be helpful for finding future cancer therapeutic targets in prostate cancer cells.close