Neem Tree Extract Halts Pancreatic Cancer Growth in Mouse Models

Nimbolide, a compound extracted from the leaves of the neem tree (Azadirachta indica), was shown in culture and mouse models to have potential as a chemotherapeutic agent for the treatment of pancreatic cancer.

The mortality and morbidity rates of pancreatic cancer are high (94% of patients die within five years of diagnosis) due to its extremely invasive and metastatic nature. Absence of symptoms, late diagnosis, chemo-resistance, and lack of effective treatment warrant the development of new chemotherapeutic agents.

Compounds from medicinal plants have demonstrated therapeutic benefits in various human cancers. Among them are nimbolide, a triterpenoid present in the edible parts of the neem tree, which displays a variety of biological activities including antimalarial and anticancer properties. Recently it was shown that nimbolide sensitized colon cancer cells to apoptosis through three distinct mechanisms: production of reactive oxygen species, downregulation of cell survival proteins, and upregulation of pro-apoptotic proteins. Products made from neem trees have been used in India for over two millennia for their medicinal properties. Neem products are believed to be anthelminthic, antifungal, antidiabetic, antibacterial, antiviral, contraceptive, and sedative. Neem oil is used for healthy hair, to improve liver function, detoxify the blood, and balance blood sugar levels. Neem leaves have also been used to treat skin diseases such as eczema and psoriasis.

Investigator at the Texas Tech University Health Sciences Center (El Paso, USA) evaluated the potential of nimbolide for the treatment of pancreatic cancer.

They reported in the January 25, 2016, online edition of the journal Scientific Reports that nimbolide induced 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 and metastasis via mitochondrial-mediated apoptotic cell death but not via autophagy.

Experiments conducted on mice demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis without harming normal, healthy cells.

"Nimbolide seems to attack pancreatic cancer from all angles," said senior author Dr. Rajkumar Lakshmanaswamy, associate professor of biomedical sciences at the Texas Tech University Health Sciences Center. "The promise nimbolide has shown is amazing, and the specificity of the treatment towards cancer cells over normal cells is very intriguing."

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Texas Tech University Health Sciences Center