Identification of PDCD2 as a Candidate Target of Andrographolide That Arrests the Tumor Cell Cycle by Human Proteome-Scale Screening.

Abstract

Andrographolide (andro) and its derivatives have been reported to have antitumor activity by arresting the cell cycle. However, the more precise mechanism has been controversial. Here, a proteome chip was used to screen drug targets in cells, and we discovered that andro can bind to PDCD2 (PD2), which has been shown to be associated with the cell cycle and mRNA nuclear export. Then, RNA-binding protein immunoprecipitation for PD2 was used to detect the quantity of cell cycle-related mRNAs, and the nuclear distribution difference analyses of these mRNAs in tumor cells after andro intervention, followed by systematic experiments, were performed to assess the downstream effects of this event in vivo and in vitro. Thus, the target spectrum of andro was revealed at the level of the human proteome chip for the first time, and this work demonstrated that andro, through targeting PD2, blocks the nuclear output of CDK mRNAs in the nucleus of tumor cells, further reduces the expression of cell CDK proteins, and finally causes tumor cell cycle arrest in phenotype and tumor tissue growth arrest in vivo.