Our laboratory has been evaluating the effects of pomegranate juice extract (PJE) in inhibiting pancreatic cancer cell growth, the fourth leading cause of cancer death in the United States. There have been several published reports indicating that phytochemicals in fruits can reduce the risk of cancer due to their polyphenol anti-oxidant and anti-inflammatory effects. Pomegranate, from the tree Punica granatum, possesses many polyphenols which makes it a valuable agent in cancer therapies. Previous reported studies using pomegranate juice (PJ) and pomegranate juice extract have shown promising results in suppressing colon, breast, lung, skin, and prostate cancer cell growth. Our lab has previously shown that PJ and PJE have anti-proliferative and pro-apoptotic effects in human COLO-357 pancreatic cancer cells. In addition, we observed that when treated with 10-25 µg/mL of PJE, cells become more adhesive, since they are harder to detach from the cell culture plate. It has been reported by other groups that low expression of Epithelial cadherin (E-cadherin) protein correlates with increased pancreatic cancer cell proliferation and metastasis. We hypothesized that treating human pancreatic cancer cells with low concentrations of PJE would increase cell adhesion by increasing E-cadherin protein levels. Another purpose of this project was to determine whether a particular polyphenol in commercial POMWonderful PJE was partially responsible for up-regulating E-cadherin. We characterized commercial POMWonderful pomegranate juice extracts by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) and the most abundant polyphenols identified were: ellagic acid, galloylglucose, caffeolquinic acid, ellagic acid glucose, gallagic acid, punicalin, and punicalagin. We used ellagic acid (EA) for further studies since it is the only commercially available polyphenol identified. We also used EA because a recent publication showed that EA treatment in pancreatic cancer cells resulted in decreased cell proliferation and increased apoptosis. In our current study, we used the human COLO-357 pancreatic cancer cell-line to evaluate E-cadherin protein levels following PJE or EA treatments. We showed that PJE (10-25 ug/ml; 48 hours) resulted in a significant up-regulation of E-cadherin via immunoblots. We also demonstrated that EA (10-50 uMol/L; 48 hours) resulted in up-regulation of E-cadherin but not as dramatically as with PJE treatment. In conclusion, this data shows that PJE and its main polyphenol, EA, of the commercially available POMWonderful PJE helps restore pancreatic cancer cell adhesion, thereby serving as a potential suppressor of invasion and metastasis.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 43.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO