Glabridin inhibits osteosarcoma migration and invasion via blocking the p38‐ and JNK‐mediated CREB–AP1 complexes formation

Abstract

Osteosarcoma is the most common bone malignancy, and it seriously affects the quality of life of affected children and adolescents. Glabridin (GLA), a major component of licorice root extract, has been reported to exert antitumor effects against a variety of tumor types; however, its effects on osteosarcoma have not been elucidated. In the current study, we investigate the effects and potential antimetastatic mechanisms of GLA on osteosarcoma in vitro and in vivo. Flow cytometry showed that GLA induced G2/M cell cycle phase arrest and promoted cell apoptosis. Transwell and wound-healing assays showed that GLA significantly decreased the migration and invasion of osteosarcoma cells. Further western blotting and quantitative real-time polymerase chain reaction showed that the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in MG63 and HOS cells were reduced after GLA treatment. Moreover, western blotting demonstrated that GLA downregulated the phosphorylation of p38 mitogen-activated protein kinases and c-Jun N-terminal kinase. A coimmunoprecipitation assay illustrated that formation of cAMP response element-binding protein (CREB)-activating protein 1 (AP1) complexes and the DNA binding activities of CREB and AP1 in MG63 and HOS cells were impaired following treatment with GLA. Finally, GLA inhibited tumor growth and suppressed osteosarcoma cell metastasis in vivo. Overall, our findings highlight the potential of GLA as a therapeutic agent for the prevention and treatment of tumor metastasis.

Visfatin Promotes the Metastatic Potential of Chondrosarcoma Cells by Stimulating AP-1-Dependent MMP-2 Production in the MAPK Pathway

“…Numerous transcription factor-binding sites have been reported in the 5 -regulatory region of MMP-2 [32]. AP-1 is an important transcriptional factor that regulates MMP-2 transcriptional ability and tumor metastasis [33]. We found that both AP-1 inhibitors (tanshinone IIA and curcumin) inhibited visfatin-induced facilitation of MMP-2 synthesis and chondrosarcoma cell migration.…”

TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway

“…To clarify the anticancer effect of RepSox in vivo , a xenograft model was established and randomly divided into three groups, receiving intraperitoneal administration of RepSox (5 mg/kg or 20 mg/kg every other day) or DMSO. In terms of drug concentration selection for the in vivo experiment, on the one hand, the CCK-8 data of our in vitro experiment were considered, and on the other hand, some published literature ( 26 - 28 ) on drug concentrations of other drugs in OS xenograft models was consulted. After three weeks, the tumors were removed from each nude mouse and measured ( Fig.…”

Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

“…MOL7, MOL10, MOL17 and MOL9 were reported to down-regulate MMP9 [58][59][60]. MOL1, MOL5, MOL12, MOL13, MOL15, and MOL52 showed reduction in MMP2 and MMP9 expression level [61][62][63][64][65][66]. As for HIF1A, there were seven compounds were reported to suppress the expression of HIF1A, including MOL5, MOL6, MOL9, MOL10, MOL13, MOL14, and MOL15 [67][68][69][70][71][72][73].…”