期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 16, 期 10, 页码 23405-23424出版社
MDPI
DOI: 10.3390/ijms161023405
关键词
osteosarcoma; apoptosis; endoplasmic reticulum stress; reactive oxygen species; migration
资金
- National Science Council of Taiwan [NSC-103-2314-B-341-004-MY3, NSC-102-2314-B-341-002-MY3]
- Shin-Kong Wu Ho-Su Memorial Hospital [SKH-8302-104-0301, SKH-8302-104-0302]
Osteosarcoma (OS) is a primary malignant tumor of bone and is most prevalent in children and adolescents. OS is frequently associated with pulmonary metastasis, which is the main cause of OS-related mortality. OS has a poor prognosis and is often unresponsive to conventional chemotherapy. In this study, we determined that Nimbolide, a novel anti-cancer therapy, acts by modulating multiple mechanisms in osteosarcoma cells. Nimbolide induces apoptosis by increasing endoplasmic reticulum (ER) stress, mitochondrial dysfunction, accumulation of reactive oxygen species (ROS), and finally, caspase activation. We also determined that Nimbolide inhibits cell migration, which is crucial for metastasis, by reducing the expression of integrin v5. In addition, our results demonstrate that integrin v5 expression is modulated by the PI3K/Akt and NF-B signaling cascade. Nimbolide has potential as an anti-tumor drug given its multifunctional effects in OS. Collectively, these results help us to understand the mechanisms of action of Nimbolide and will aid in the development of effective therapies for OS.
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