Figure 1. Identification of pyrvinium pamoate as an effective inhibitor of HuR.

(A) HuR ablation potentiates the efficacy of genotoxic agents. Left, HuR isogenic cell lines; right, HuR deletion potentiated chemotherapeutic efficacy in 5637 cancer cells. (B) Pyrvinium pamoate inhibits the UVC-triggered increase of HuR cytoplasmic accumulation in a concentration-dependent manner. (C) Pyrvinium pamoate blocks genotoxic agent-triggered cytoplasmic translocation of HuR. 5637 cells were treated with different genotoxic agents alone or in combination with 100 nmol/L of pyrvinium pamoate for 48 h. (D) Pyrvinium pamoate blocks doxorubicin-triggered cytoplasmic accumulation of HuR by immunofluorescence. (E) HuR-null cells are more resistant to pyrvinium pamoate's treatment compared to their wild-type counterparts. IC₅₀s were calculated by GraphPad Prism Software. Dot, mean; bars, standard deviation. CE, cytoplasmic extracts; WCE, whole-cell extracts; PP, pyrvinium pamoate; CDDP, cisplatin; Oxa, oxaliplatin; Dox, doxorubicin; VCR, vincristine; Gem, gemcitabine; wt, wild-type; K.O., knockout.