Pomegranates and Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease in which the overall five year survival rate is approximately 3-5%.  The diagnosis of pancreatic cancer is usually established at an advanced stage when the majority of patients are not candidates for surgery.  Survival is usually limited to patients who had surgery at an early stage of the disease.  Non-surgical treatment for pancreatic cancer is generally ineffective due to the resistance of pancreatic cancer cells to chemotherapy and the tumor’s ability to metastasize.   Therefore, the understanding of the molecular alterations that occur in this disease will lead to designing better chemopreventive agents as well as therapies.

Since studies have shown evidence that many cancers can be avoided by lifestyle modifications, such as diet and exercise, the demand for dietary alternatives have prompted explorative studies on phytochemicals, botanically derived disease-preventing compounds.  Phenolic acids, flavanoids, and polyphenols are subgroups of the phytochemicals known as phenolic compounds. Flavanoids (anthocyanins)) and hydrolyzable tannins (phenolic acids) are the secondary plant metabolites responsible for 92% of the antioxidant activity of the whole pomegranate fruit.  Their ability to act as antioxidants makes them valuable agents in cancer therapies.  Previous reported studies have focused on testing the effects of pomegranate juice in skin, colon, breast, lung, and prostate cancer. These studies have provided evidence for pomegranate’s anti-inflammatory, antioxidant, chemotherapeutic, chemopreventive, anti-proliferative, anti-angiogenic and pro-apoptotic properties.  The process of apoptosis (programmed cell death) is well documented and involves the following characteristics:  “non-random mono and oligonucleosomal length fragmentation of DNA, formation of apoptotic bodies and cell shrinkage due to condensation of the cytoplasm.”

 It is known that Vascular endothelial Growth Factor (VEGF) is a main inducer of angiogenesis (new blood vessel supply) and is over-expressed in pancreatic cancer which is correlated with decreased patient survival.  It is also known that E-cadherin, a cell adhesion protein, is over-expressed in pancreatic cancer. 

The main goal of our laboratory is to evaluate the extent to which polyphenolics present in pomegranate extracts can be used therapeutically to inhibit pancreatic cancer cell growth in vitro.  We hypothesize that: A. treatment of pancreatic cancer cells with Pom Wonderful Pomegranate Extract (PE) decreases cell proliferation by triggering apoptosis; B. PE inhibits angiogenesis by inhibiting VEGF protein levels; C.  PE promotes the up-regulation of the E-cadherin protein involved in cell adhesion.  By becoming more adhesive, the cells lose their ability to be motile and therefore become less invasive. Lastly, we want to investigate if PE modulates proteins involved in various signal transduction pathways.

Faculty:  Dr. Melissa Rowland-Goldsmith, Department of Biological Sciences