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Int. J. Mol. Sci. 2015, 16(10), 23405-23424; doi:10.3390/ijms161023405

Nimbolide Induces ROS-Regulated Apoptosis and Inhibits Cell Migration in Osteosarcoma

1
Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan
2
Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei 10617, Taiwan
3
Department of Dermatology, Sijhih Cathay General Hospital, Taipei 22174, Taiwan
4
Department of Orthopedic Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Road, Shilin District, Taipei 11101, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 22 June 2015 / Revised: 5 September 2015 / Accepted: 21 September 2015 / Published: 29 September 2015
(This article belongs to the Collection Advances in Molecular Oncology)
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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. View Full-Text
Keywords: osteosarcoma; apoptosis; endoplasmic reticulum stress; reactive oxygen species; migration osteosarcoma; apoptosis; endoplasmic reticulum stress; reactive oxygen species; migration
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Liu, J.-F.; Hou, C.-H.; Lin, F.-L.; Tsao, Y.-T.; Hou, S.-M. Nimbolide Induces ROS-Regulated Apoptosis and Inhibits Cell Migration in Osteosarcoma. Int. J. Mol. Sci. 2015, 16, 23405-23424.

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