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Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/?-catenin pathway in vitro and in vivo.

ABSTRACT: Osteosarcoma is the most common primary bone cancer in children and adolescents. In spite of aggressive treatment, osteosarcoma has a high mortality rate with minimal improvements in survival over past few decades. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb Paris polyphylla Smith, has been shown to have anti-tumor properties. However, its mechanism as an anti-osteosarcoma agent has not been well elucidated. In this study, we found that PPI suppressed osteosarcoma cell viability, arrested cell cycle in G₂/M phase, induced apoptosis and inhibited invasion and migration of osteosarcoma cells. Moreover, PPI significantly suppressed intratibial primary tumor growth in xenograft orthotopic mouse model without any obvious side effects. These therapeutic efficacies were associated with inactivation of Wnt/?-catenin pathway, as PPI treatment decreased the amount of p-GSK-3?, leading to down-regulated levels of active ?-catenin. PPI induced inhibition of osteosarcoma cell viability was abolished upon addition of GSK-3? specific inhibitor, CHIR99021, while PPI induced inhibition of osteosarcoma cell viability and migration were potentiated by ?-catenin silencing. These findings suggested that, in vitro and in vivo, PPI treatment inhibited osteosarcoma, at least in part, via the inactivation of Wnt/?-catenin pathway. Thus, PPI could serve a novel therapeutic option for osteosarcoma patients.

SUBMITTER: Chang J

PROVIDER: S-EPMC5548759 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo.

Chang Junli J Li Yimian Y Wang Xianyang X Hu Shaopu S Wang Hongshen H Shi Qi Q Wang Yongjun Y Yang Yanping Y

Scientific reports 20170808 1

Osteosarcoma is the most common primary bone cancer in children and adolescents. In spite of aggressive treatment, osteosarcoma has a high mortality rate with minimal improvements in survival over past few decades. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb Paris polyphylla Smith, has been shown to have anti-tumor properties. However, its mechanism as an anti-osteosarcoma agent has not been well elucidated. In this study, we found that PPI suppressed osteosarcoma ...[more]

PMID: 28790389

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Project description:BackgroundAlthough there are many treatments for breast cancer, such as surgery, radiotherapy, chemotherapy, estrogen receptor antagonists, immune checkpoint inhibitors and so on. However, safer and more effective therapeutic drugs for breast cancer are needed. Sinensetin, a safer therapeutic drugs, come from citrus species and medicinal plants used in traditional medicine, while its role and underlying mechanism in breast cancer remain unclear. Our study aimed to investigate the role and mechanism of sinensetin in breast cancer.MethodsCell Counting Kit-8 (CCK-8) was used to determine the safe concentration of sinensetin in MCF-10A, MCF7 and MDA-MB-231 cells; 120 μM sinensetin was used in subsequent experiments. Real time polymerase chain reaction (RT-PCR), Western blotting, Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay, Transwell invasion assay and Clone formation assay were used in this study to determine cell viability, mRNA expression, protein levels, apoptosis, proliferation, invasion and so on.ResultsHerein, our results showed that 120 μM sinensetin suppressed the cell viability and promoted apoptosis of MCF7 and MDA-MB-231 cells. Treatment with 120 µM sinensetin for 24 h showed no significant toxicity to normal mammary cells; 120 μM sinensetin decreased cell proliferation, invasion, and epithelial-mesenchymal transition (EMT), and downregulated β-catenin, lymphatic enhancing factor 1 (LEF1), T-cell factor (TCF) 1/TCF7, and TCF3/TCF7L1 expression in MCF7 and MDA-MB-231 cells. The Wnt agonist SKL2001 reversed the inhibitory effect of sinensetin on cell survival, metastasis, and EMT. Sinensetin-induced downregulation of β-catenin, LEF1, and TCF1/TCF7 expression were upregulated by SKL2001 in MCF7 and MDA-MB-231 cells.ConclusionsIn summary, sinensetin suppressed the metastasis of breast cancer cell via inhibition of Wnt/β-catenin pathway and there were no adverse effects on normal breast cells. Our study confirmed the role of sinensetin in breast cancer cells and provided a better understanding of the underlying mechanism.

Dataset Information

Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/?-catenin pathway in vitro and in vivo.

Publications

Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo.

Similar Datasets

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