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Sci Rep. 2016 Jan 25;6:19819. doi: 10.1038/srep19819.

Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition.

Author information

1
Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas-79905.
2
Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, Texas-79905.
3
The University of Texas at El Paso, El Paso, TX 79968.
4
Biostatistics and Epidemiology Consulting Laboratory, Texas Tech University Health Sciences Center, El Paso, Texas-79905.

Abstract

The mortality and morbidity rates of pancreatic cancer are high because of its extremely invasive and metastatic nature. Its lack of symptoms, late diagnosis and chemo-resistance and the ineffective treatment modalities warrant the development of new chemo-therapeutic agents for pancreatic cancer. Agents from medicinal plants have demonstrated therapeutic benefits in various human cancers. Nimbolide, an active molecule isolated from Azadirachta indica, has been reported to exhibit several medicinal properties. This study assessed the anticancer properties of nimbolide against pancreatic cancer. Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. Experiments with the autophagy inhibitors 3-methyladenine and chloroquine diphosphate salt and the apoptosis inhibitor z-VAD-fmk demonstrated that nimbolide-mediated ROS generation inhibited proliferation (through reduced PI3K/AKT/mTOR and ERK signaling) and metastasis (through decreased EMT, invasion, migration and colony forming abilities) via mitochondrial-mediated apoptotic cell death but not via autophagy. In vivo experiments also demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis. Overall, our data suggest that nimbolide can serve as a potential chemo-therapeutic agent for pancreatic cancer.

PMID:
26804739
PMCID:
PMC4726267
DOI:
10.1038/srep19819
[Indexed for MEDLINE]
Free PMC Article

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