The effect of pomegranate juice extract on the Hedgehog signaling pathway in pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer death in the United States. There have been several reports indicating that phytochemicals in fruits can reduce the risk of cancer due to the anti-oxidant and anti-inflammatory effects of the polyphenols. Our lab has shown that pomegranate juice extract (PJE) has anti-proliferative and pro-apoptotic effects in human pancreatic cancer cells. In the past, we have shown that cells adhere more strongly to the plate when treated with PJE. This observation prompted an investigation of how PJE regulates cell adhesion proteins. Previously, our lab investigated E-cadherin, a cell adhesion protein. Upon activation of the Hedgehog signaling pathway, Gl-1 has been shown to down-regulate E-cadherin. The purpose of this study was to determine if PJE up-regulates ezrin, another cell adhesion protein, by interfering with the Gl-1 transcription factor of the Hedgehog signaling cascade. Through the use of immunoblots, we evaluated Gl-1 and ezrin protein levels after PJE treatment in COLO-357 human pancreatic cancer cells. We showed that pancreatic cancer cells treated with PJE led to decreased expression of Gl-1 and up-regulation of ezrin. This data suggests that PJE can help restore pancreatic cancer cell adhesion by blocking an important signaling pathway, thus serving as a potential suppressor of invasion and metastasis