Abstract
Ellagic aicd (EA), a dietary polyphenolic compound found in plants and fruits, possesses various pharmacological activities. This study investigated the effect of EA on human pancreatic carcinoma PANC-1 cells both in vitro and in vivo; and defined the associated molecular mechanisms. In vitro, the cell growth and repairing ability were assessed by CCK-8 assay and wound healing assay. The cell migration and invasion activity was evaluated by Tanswell assay. In vivo, PANC-1 cell tumor-bearing mice were treated with different concentrations of EA. We found that EA significantly inhibited cell growth, cell repairing activity, and cell migration and invasion in a dose-dependent manner. Treatment of PANC-1 xenografted mice with EA resulted in significant inhibition in tumor growth and prolong mice survival rate. Furthermore, flow cytometric analysis showed that EA increased the percentage of cells in the G1 phase of cell cycle. Western blot analysis revealed that EA inhibited the expression of COX-2 and NF-κB. In addition, EA reversed epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. In summary, the present study demonstrated that EA inhibited cell growth, cell repairing activity, cell migration and invasion in a dose-dependent manner. EA also effectively inhibit human pancreatic cancer growth in mice. The anti-tumor effect of EA might be related to cell cycle arrest, down-regulating the expression of COX-2 and NF-κB, reversing epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. Our findings suggest that the use of EA would be beneficial for the management of pancreatic cancer.
Highlights
Pancreatic cancer ranks the fourth most deadly form of cancer in the United States and it has a poor prognosis with a 5-year survival rate of less than 5% [1]
Because pancreatic cancer is hypovascular with a dense fibrous capsule on the surface, chemotherapeutic drugs are difficult to permeate to the tumor
The present study investigated the effect of the natural drug Ellagic aicd (EA) on human pancreatic carcinoma PANC-1 cells and pancreatic xenograft tumor in Balb c nude mice
Summary
Pancreatic cancer ranks the fourth most deadly form of cancer in the United States and it has a poor prognosis with a 5-year survival rate of less than 5% [1]. Ellagic acid (EA), a natural dietary polyphenolic compound, is present in several plants and fruits, including pomegranates, strawberries, raspberries and blackberries [4]. It has antioxidant, antifibrosis, and anticarcinogenic properties [5,6,7]. The anticarcinogenic effect of EA was shown in several types of cancers including colon, breast, and prostate cancers [8]. In spite of these findings, the effects of EA on pancreatic cancer have not been studied. The mechanisms mediating anticancer effect of EA remain unknown
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