Nimbolide induces ROS-regulated apoptosis and inhibits cell migration in osteosarcoma

Ju Fang Liu, Chun Han Hou, Feng Ling Lin, Ya Ting Tsao, Sheng Mou Hou

研究成果: 雜誌貢獻文章同行評審

21 引文 斯高帕斯(Scopus)

摘要

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 αvβ5. In addition, our results demonstrate that integrin αvβ5 expression is modulated by the PI3K/Akt and NF-κB 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.
原文英語
頁(從 - 到)23405-23424
頁數20
期刊International Journal of Molecular Sciences
16
發行號10
DOIs
出版狀態已發佈 - 一月 1 2015

ASJC Scopus subject areas

  • 催化
  • 分子生物學
  • 光譜
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學
  • 無機化學

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