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.