Undecylprodigiosin induced apoptosis in P388 cancer cells is associated with its binding to ribosome

Abstract

Prodigiosins (PGs) are a family of natural red pigments with anticancer activity, and one member of the family has entered clinical phase II trials. However, the anticancer mechanisms of PGs remain largely unclear. This study was designed to investigate the molecular basis of anticancer activity of UP, a derivative of PGs, in P388 cells. By introducing pharmacological inhibitors and utilizing a variety of analytical approaches including western blotting, flow cytometry and confocal laser microscopy, we found that UP inhibited proliferation of P388 via arresting cells at G2/M phase and inducing cells apoptosis, which was related to the activation of P38, JNK rather than ERK1/2 signaling. ROS regeneration and acidification in cells appear not involved in UP induced apoptosis. Furthermore, utilizing mass spectrometry, sucrose density gradient fractionation and immunofluorescence staining, we discovered that UP was apparently located at ribosome. These results together indicate that ribosome may be the potential target of UP in cancer cells, which opened a new avenue in delineating the anticancer mechanism of PGs.