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Introduction
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. As one of the most aggressive human cancers, the 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is <5% (1). Recent studies suggested that bioactive compounds from mushrooms could protect against multiple myeloma, breast and skin cancer (2–5). Poria cocos (also known as Wolfiporia extensa) is a medicinal mushroom in the Polyporaceae family that grows in pine trees and its sclerotium is widely used in traditional Asian medicine for its sedative, diuretic, digestive and tonic effects (6–8). Although the anticancer activity of polysaccharides extracted from P. cocos is associated with the stimulation of immune response and these polysaccharides significantly enhance immunopotentiation (9), triterpenes isolated from P. cocos have a direct inhibitory effect on cancer cells through a variety of mechanisms including inhibition of cell proliferation, induction of apoptosis and suppression of invasive behavior (10–16). However the effect of triterpenes from P. cocos against pancreatic cancer remains to be evaluated and the mechanism determined.
In the present study, we evaluated the effects of a triterpene mixture extracted from P. cocos (PTE) and three purified triterpenes: pachymic acid (PA), dehydropachymic acid (DPA) and polyporenic acid C (PPAC), on growth and invasive behavior of human pancreatic cancer cell lines Panc-1, MiaPaca-2, BxPc-3 and AsPc-1 and normal pancreatic duct epithelial cell line HPDE-6. PTE as well as PA, DPA and PPAC inhibit growth of pancreatic cancer cells and PTE and PA significantly suppress invasive behavior of BxPc-3 cells by inhibiting expression of MMP-7. Taken together, our results indicate that triterpenes from P. cocos may be potentially exploited for the use in pancreatic cancer intervention.
Materials and methods
Reagents
Dried sclerotium of P. cocos from Fujian, P.R. China was provided by Professor Zhonglin Yang (China Pharmaceutical University, Nanjing, P.R. China). It was authenticated by School of Traditional Chinese Medicine at China Pharmaceutical University. Voucher specimens were deposited at State Key Laboratory of Natural Medicines, China Pharmaceutical University. DMSO was purchased from Sigma (St. Louis, MO). All other chemicals and reagents were of analytical grade. Anti-MMP-7 and anti-β-actin antibodies were obtained from Santa Cruz Biotechnology (Santa Cruz, CA).
Extraction and purification
Pulverized sclerotium of P. cocos (2.0 kg) was extracted three times with 95%...