RRC ID 76678
Author Higuchi T, Takeuchi A, Munesue S, Yamamoto N, Hayashi K, Harashima A, Yamamoto Y, Tsuchiya H.
Title A nonsteroidal anti-inflammatory drug, zaltoprofen, inhibits the growth of extraskeletal chondrosarcoma cells by inducing PPARγ, p21, p27, and p53.
Journal Cell Cycle
Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and master transcription factor of adipogenesis-related genes, and has been reported as an antitumor target for chondrosarcomas. Herein, we show that the nonsteroidal anti-inflammatory drug, zaltoprofen, induces the expression of PPARγ at the mRNA and protein levels, following the induction of PPARγ-activating factors, such as Krox20, C/EBPβ, and C/EBPα, in human extraskeletal chondrosarcoma H-EMC-SS cells. Upregulation of the cell cycle checkpoint proteins, p21, p27, and p53, was observed upon treatment of H-EMC-SS cells with zaltoprofen, which probably resulted in the inhibition of proliferation of these cells observed in vitro. Zaltoprofen treatment inhibited tumor growth, induced tumor cell apoptosis, and was well tolerated in a mouse model of extraskeletal myxoid chondrosarcoma. Our results provide mechanistic insights into the therapeutic effect of zaltoprofen that should promote further studies on the rational use of this drug for the effective treatment of sarcomas.
Volume 22(8)
Pages 939-950
Published 2023-4-1
DOI 10.1080/15384101.2023.2166195
PMID 36636023
PMC PMC10054153
MeSH Animals Anti-Inflammatory Agents Cell Cycle Proteins / metabolism Chondrosarcoma* / drug therapy Chondrosarcoma* / metabolism Chondrosarcoma* / pathology Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Humans Mice PPAR gamma* / metabolism Tumor Suppressor Protein p53 / genetics
IF 3.699
Human and Animal Cells H-EMC-SS(RCB0508)