Inhibitory effects of sphingosine 1-phosphate on proliferation of PC-3 human prostate cancer cells

Inhibitory effects of sphingosine 1-phosphate on proliferation of PC-3 human prostate cancer cells. Zoological Studies 44(2): 219-227. Prostate cancer is the most-common cancer in adult men and the 2nd-leading cause of cancer deaths in Western countries. Although androgens and peptide growth factors have been implicated in this disease, determinants of the pathologic growth of prostate cancer are still unclear. Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both potent lysophospholipid growth factors with diverse biological activities and have been suggested as being important in regulating the proliferation and metastasis of cancer cells. LPA activates the ERK pathway and induces proliferation of the human prostate cancer cell line, PC-3. However, the effect of S1P on prostate cancer is still poorly understood. In this study, we found that S1P inhibited cell proliferation through an apoptosis-independent and necrosis-dependent mechanism and caused cell cycle arrest in the G, phase of PC-3 cells. S1P also induced significant rounding of cells and actin reorganization. These effects are likely mediated through activation of the S1P(5) receptor. In conclusion, we propose that S1P might change cell-ECM interactions through cytoskeletal rearrangement, thereby influencing the proliferation of prostate cancer cells.