Honokiol Induces Calpain-Mediated Glucose-Regulated Protein-94 Cleavage and Apoptosis in Human Gastric Cancer Cells and Reduces Tumor Growth

摘要: Background. Honokiol, a small molecular weight natural product, has been shown to possess potent anti-neoplastic and antiangiogenic properties. Its mechanisms the ability of anti-gastric cancer remain unknown. It that anti-apoptotic function glucose-regulated proteins (GRPs) predicts their induction in neoplastic cells can lead progression drug resistance. We explored effects honokiol on regulation GRPs apoptosis human gastric tumor growth. Methodology Principal Findings. Treatment various with led GRP94 cleavage, but did not affect GRP78. Silencing by interfering RNA (siRNA) could induce cell apoptosis. or chemotherapeutics agent etoposide enhanced increase degradation. The calpain activity calpain-II (m-calpain) protein (but calpain-I (mcalpain)) level also be increased honokiol. Honokiol-induced down-regulation reversed siRNA targeting inhibitors. Furthermore, results immunofluorescence staining immunoprecipitation revealed specific interaction following treatment. next observed over-expression growth BALB/c nude mice, which were inoculated MKN45, are markedly decreased Conclusions Significance. These provide first evidence honokiol-induced calpain-II-mediated cleavage causes further suggest may possible therapeutic improve clinical outcome cancer. Citation: Sheu ML, Liu SH, Lan KH (2007) Honokiol Induces Calpain-Mediated Glucose-Regulated Protein-94 Cleavage Apoptosis Human Gastric Cancer Cells Reduces Tumor Growth. PLoS ONE 2(10): e1096. doi:10.1371/journal.pone.0001096