Nimbolide induces ROS-regulated apoptosis and inhibits cell migration in osteosarcoma
Journal
International Journal of Molecular Sciences
Journal Volume
16
Journal Issue
10
Pages
23405-23424
Date Issued
2015
Author(s)
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. ? 2015 by the authors; licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
2 morpholino 8 phenylchromone; acetylcysteine; beta5 integrin; calcium ion; calpain; caspase; caspase 3; caspase 9; CD51 antigen; hydrogen peroxide; I kappa B; lipocortin 5; nimbolide; phosphatidylinositol 3 kinase; propidium iodide; protein bcl 2; protein kinase B; reactive oxygen metabolite; tosylphenylalanyl chloromethyl ketone; alphaVbeta5 integrin; calcium; caspase; immunoglobulin enhancer binding protein; limonoid; nimbolide; phosphatidylinositol 3 kinase; protein kinase B; reactive oxygen metabolite; vitronectin receptor; apoptosis; Article; cell culture; cell death; cell invasion assay; cell migration; cell signaling assay; cell survival; colony formation; controlled study; cytochemistry; DNA fragmentation assay; endoplasmic reticulum stress; enzyme activity; human; human cell; metastasis; mitochondrial membrane potential; MTT assay; osteosarcoma; protein expression; signal transduction; TUNEL assay; Western blotting; apoptosis; cell motion; chemistry; drug effects; enzyme activation; metabolism; mitochondrion; osteosarcoma; pathology; tumor cell line; Apoptosis; Calcium; Caspases; Cell Line, Tumor; Cell Movement; Endoplasmic Reticulum Stress; Enzyme Activation; Humans; Limonins; Mitochondria; NF-kappa B; Osteosarcoma; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Receptors, Vitronectin; Signal Transduction
Publisher
MDPI AG
Type
journal article