Ellagic acid inhibits the proliferation of human pancreatic carcinoma PANC-1 cells in vitro and in vivo

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.

Rapid Screening of Ellagitannins in Natural Sources via Targeted Reporter Ion Triggered Tandem Mass Spectrometry

“…The smallest ellagitannin, 2,3-hexahydroxydiphenoylglucose, is defined from the condensation of single HHDP and glucose subunits (482.070 Da) but whether to include species with molecular weights lower than this when reporting ellagitannins has not yet been standardized 62 , 68 . A targeted mass exclusion list was initially considered to ensure no singly charged m/z below 481.062 would be included for precursor selection, but was not added to the method parameters given general interest and precedent set by recent studies 62 , 69 – 72 . Species below 482.070 Da were omitted from T-2RT enumeration (Table 2 ) to accurately report ellagitannin summary values in addition to the aforementioned adjustments for charge state and isotope duplicates.…”

A Pharmacological Update of Ellagic Acid

“…Ellagic acid also seems to inhibit the growth, ability to repair, migration, and invasion of human pancreatic carcinoma PANC-1 cells in a dose dependent manner. Thus, PANC-1 cell tumor-bearing mice treated with ellagic acid had an increased survival rate, with inhibition of tumor growth through cell cycle arrest in the G 1 phase; downregulation of COX-2, NF-κB, and vimentin; and upregulation of E-cadherin [188].…”

Urolithin A, a Novel Natural Compound to Target PI3K/AKT/mTOR Pathway in Pancreatic Cancer

“…Ellagitannins are hydrolyzed in the gut to release ellagic acid (EA), a compound which inhibits multiple oncogenic pathways which are activated in PDAC such as COX-2, NF-kB, Notch, and Wnt signaling. Preclinical studies have shown that targeted blockade of these pathways by EA is successful in reducing epithelial-mesenchymal transition, angiogenesis, fibrosis, and pancreatic stellate cell activation in PDAC (8,9). Despite these promising developments, EA is unfortunately poorly absorbed within the human gut, limiting its efficacy as a therapeutic agent.…”

“…Uro A has been shown to downregulate multiple tumor pathways in colon, prostate, and bladder cancer through downregulation of several oncogenes such as Kras and c-myc, upregulation of tumor-suppressor genes such as FGFR2 and EGFR, and modulation of enzyme activity, such as CYP1 (13). Despite the promising effects seen in treating other malignancies, the anticancer effect of Uro A in PDAC is currently unknown (8,9).…”