Inhibition of Plk1 and Pin1 by 5'-nitro-indirubinoxime suppresses human lung cancer cells.

A novel indirubin derivative, 5'-nitro-indirubinoxime (5'-NIO), exhibits a strong anti-cancer activity against human cancer cells. Here, the 5'-NIO-mediated G1 cell cycle arrest in lung cancer cells was associated with a decrease in protein levels of polo-like kinase 1 (Plk1) and peptidyl-prolyl cis/trans isomerase Pin1. Treatment with Plk1 siRNA or Pin1 inhibitor effectively inhibited the Rb phosphorylation, suggesting their regulatory role at G1 phase. In addition, the overexpression of Plk1 or Pin1 inhibited apoptotic signals following the cleavage of PARP in 5'-NIO-treated cells. These findings suggest that 5'-NIO have potential anti-cancer efficacy through the inhibition of Plk1 or/and Pin1 expression.