Ciclopirox inhibits cancer cell proliferation by suppression of Cdc25A.

ABSTRACT: Ciclopirox olamine (CPX), an off-patent fungicide, has recently been identified as a novel anticancer agent. However, the molecular mechanism underlying its anticancer action remains to be elucidated. Here we show that CPX inhibits cell proliferation in part by downregulating the protein level of Cdc25A in tumor cells. Our studies revealed that CPX did not significantly reduce Cdc25A mRNA level or Cdc25A protein synthesis, but remarkably promoted Cdc25A protein degradation. This resulted in inhibition of G₁-cyclin dependent kinases (CDKs), as evidenced by increased inhibitory phosphorylation of G₁-CDKs. Since Cdc25A degradation is tightly related to its phosphorylation status, we further examined whether CPX alters Cdc25A phosphorylation. The results showed that CPX t

SUBMITTER: Shen T 

PROVIDER: S-EPMC5489648 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature