Scytonemin inhibits cell proliferation and arrests cell cycle through downregulating Plk1 activity in multiple myeloma cells

Abstract

Multiple myeloma is the second most common hematologic malignancy. During the pursuit for novel and more selective anticancer drugs, different approaches have pointed to polo-like kinase 1 (Plk1) as a promising target. So we used a novel agent, scytonemin, to inhibit the activity of Plk1 to investigate the effect of Plk1 in multiple myeloma cells. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to examine the effect of scytonemin on the cell proliferation of three multiple myeloma cell lines with different concentration and different time. Flow cytometry was used to examine the effect of scytonemin on the cell cycle of multiple myeloma U266 cells with different concentration and different time. Moreover, the expression of Plk1 was analyzed by Western blot and real-time PCR in myeloma U266 cells with the treatment of scytonemin. Statistical analysis was used to analyze the effect of scytonemin on the cell proliferation and cell cycle with different concentration and different time and the association between Plk1 expression and activity with the treatment of scytonemin. Scytonemin was able to inhibit the proliferation of three myeloma cells in a dose-dependent manner, while U266 was the most sensitive one to scytonemin. Treatment with 3 and 4 μM scytonemin gradually increased the percentage of cells in the G2-M phase in U266 cells upon 48- and 72-h treatment. Scytonemin (at 3 and 4 μM concentration) inhibited multiple myeloma cell growth associated with downregulation of the activity of Plk1 but no effect on the expression of Plk1. Scytonemin, representing a novel Plk1 inhibitor, induced the inhibition of cell growth and cell cycle arrest in multiple myeloma cells by specifically decreasing Plk1 activity. Taken together, scytonemin is a promising novel agent for the treatment of multiple myeloma.