The anti-proliferative, pro-apoptotic, and anti-angiogenic effects of polyphenol rich pomegranate juice and pomegranate extract on COLO-357 pancreatic cancer cells

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Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that is the fourth leading cause of cancer death in the United States. PDAC exhibits the “classic hallmarks of cancer” including evasion of apoptosis and sustained angiogenesis. There is strong evidence that the phytochemicals in fruits can reduce the risk of cancer due to their polyphenol anti-oxidant and anti-inflammatory effects. Thus, the demand for dietary alternatives has prompted explorative studies on phytochemicals. Pomegranate, from the tree Punica granatum, possesses many polyphenols. The ability of this fruit to act as an antioxidant makes it a valuable agent in cancer therapies. Previous reported in vitro and in vivo studies have focused on testing the effects of pomegranate juice (PJ) and pomegranate extract (PE) in colon, breast, lung, and prostate cancer and have shown promising results in suppressing cancer growth. At this time, testing with PJ and PE has yet to be done in pancreatic cancer cell lines. It has been shown that Vascular Endothelial Growth Factor (VEGF), a pro-angiogenic factor, is over-expressed in PDAC and its over-expression is correlated with decreased patient survival. We hypothesized that treatment of pancreatic cancer cells with PJ and PE would decrease cell proliferation by triggering apoptosis and also inhibit angiogenesis by decreasing VEGF protein levels. Using COLO-357 human pancreatic cancer cells, we evaluated the anti-proliferative, pro-apoptotic, and anti-angiogenic properties of PJ and PE. In this study, we showed that PJ (percent volumes ranging from 0.1-4%; 48 hours) and PE (25-50 ug/ml; 48 hours) resulted in a significant dose dependent inhibition of cell growth via cell growth assays. We also reported through DNA laddering techniques that genomic DNA isolated from cancer cells treated with PE (10-50 ug/ml; 48 hours) showed laddering characteristic of apoptosis. It was also shown through immunoblotting techniques that there was a decrease in VEGF expression in cancer cells treated with PJ (percent volumes ranging from 0.05% to 0.25%; 48 hours) and PE (10 ug/ml; 48 hours). These preliminary results warrant further investigation of PJ and PE as potential therapeutic agents against PDAC.