A Nonsteroidal Anti-inflammatory Drug, Zaltoprofen, Inhibits the Growth of Extraskeletal Chondrosarcoma Cells by Inducing PPARγ, p21, p27, and p53

Abstract There is no effective treatment except surgical resection for extraskeletal myxoid chondrosarcoma (EMC). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and a master transcription factor of adipogenesis-related genes and has been reported as an antitumor target for chondrosarcomas. Herein, we show that a nonsteroidal anti-inflammatory drug, zaltoprofen, induces the expression of PPARγ at mRNA and protein levels, following the induction of PPARγ-activating factors, such as Krox20, C/EBPβ, and C/EBPα, in human extraskeletal chondrosarcoma cells, H-EMC-SS. Zaltoprofen inhibited the proliferation of these cells in vitro. Upregulation of cell cycle checkpoint proteins, p21, p27, and p53, was observed upon treatment of cells with zaltoprofen, which probably resulted in the inhibition of proliferation of H-EMC-SS cells. Zaltoprofen treatment induced tumor necrosis, which could be due to its antiproliferative properties, and was well tolerated in a mouse model of EMC. Our results provide mechanistic insights into the therapeutic effect of zaltoprofen that should promote further studies on the rational use of this drug for effective treatment of EMC.