Pomegranate Extract Induces Cell Cycle Arrest and Alters Cellular Phenotype of Human Pancreatic Cancer Cells

Background: Pomegranate extract (PE) is a standardized whole-fruit extract of pomegranate, a fruit with known anticancer properties. Materials and Methods: PANC- 1 and AsPC-1 human pancreatic cancer cells were used as in vitro models to test the effects of PE. Results: PE treatment induced cell cycle arrest and inhibited cell proliferation in PANC-1 cells. PE treatment increased the proportion of cells lacking CD44 and CD24 expression, which are associated with increased tumor-initiating ability, demonstrating that PE altered cell phenotype. PE was more effective in inhibiting the proliferation of PANC-1 cells than the clinically used dose of paclitaxel. Similar results were obtained in the AsPC-1 cell line. Individual pomegranate phytochemicals were only modestly effective in inhibiting cell proliferation, suggesting that unidentified phytochemicals are responsible for the inhibitory effect of PE. Conclusion: These data suggest that PE is a promising candidate for further preclinical testing for treatment of human pancreatic cancer. Pancreatic cancer, one of the most lethal forms of cancer, is the fourth leading cause of cancer death in both genders. The poor prognosis of pancreatic cancer patients is due to often late- stage diagnosis, and the ineffectiveness of current chemotherapeutic regimens. 5-fluorouracil and gemcitabine are the only chemotherapeutic agents that have been successful in the treatment of pancreatic cancer, but their efficacy is low and they cause serious side-effects (1). Therefore, the identification and development of alternative medicines for the treatment and prevention of pancreatic cancer is needed. Dietary sources are a promising source of new therapeutic options. Pomegranate (Punica granatum) is a fruit used in many cultures (the genus name, Punica, is derived from the Roman name for Carthage, where the best pomegranates were known to grow). The pomegranate tree is native to the region of Persia and is now cultivated over the entire Mediterranean area, Asia, and America. Pomegranate extract (PE) consists of a mixture of various phytochemicals, including the punicalagins, a class of tannins unique to pomegranates, which have been shown to possess free radical-scavenging properties (2, 3). Pomegranate has been valued in many cultures for millennia for its therapeutic attributes, including anti-inflammatory, anti- hypertensive, and anti-diabetic properties (4). Recent studies have shown that pomegranate is a potent anticancer agent that causes the induction of apoptosis and cell cycle arrest in cancer cells, inhibition of multiple signaling pathways in cancer cells, inhibitionof tumorigenesis in animal models of various carcinomas (5-8). These qualities make pomegranate a promising source of novel preventive and therapeutic agents, but its effects on pancreatic cancer have not, to the best of our knowledge, been studied. In the present study we examined the activity of a standardized, commercially available, and certified safe PE on the growth and viability of human pancreatic cancer cells in vitro. To ensure that our results were not cell line- dependent, two different human cancer cell lines were studied. We demonstrate that PE effectively inhibits the growth and viability of human pancreatic cancer cells by inducing cell cycle arrest, and reduces the tumor-initiating phenotype of the cancer cells. This is the first demonstration that PE may have efficacy against pancreatic cancer.