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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)23405-23424
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume16
Issue number10
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • Apoptosis
  • Endoplasmic reticulum stress
  • Migration
  • Osteosarcoma
  • Reactive oxygen species

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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