title: Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7.
abstract: Poria cocos is a medicinal mushroom that is widely used in traditional Asian medicine. Here, we show that a characterized mixture of triterpenes extracted from P. cocos (PTE) and three purified triterpenes: pachymic acid (PA), dehydropachymic acid (DPA) and polyporenic acid C (PPAC) suppress the proliferation of the human pancreatic cancer cell lines Panc-1, MiaPaca-2, AsPc-1 and BxPc-3. Moreover, the most effective compound, PA, only slightly affects the proliferation of HPDE-6 normal pancreatic duct epithelial cells. The anti-proliferative effects of PTE on BxPc-3 cells are mediated by the cell cycle arrest at G0/G1 phase. DNA microarray analysis demonstrated that PTE significantly downregulates the expression of KRAS and matrix metalloproteinase-7 (MMP-7) in BxPc-3 cells. In addition, PTE and PA suppress the invasive behavior of BxPc-3 cells. The inhibition of invasiveness by PTE and PA was associated with the reduction of MMP-7 at the protein level and the role of MMP-7 further confirmed by the gene silencing of MMP-7 which also suppressed the invasiveness of BxPc-3 cells. In conclusion, triterpenes from P. cocos demonstrate anticancer and anti-invasive effects on human pancreatic cancer cells and can be considered as new therapeutic agents in the treatment of pancreatic cancer.
authors.affiliation: Department of Bioengineering, College of Food Science, South China Agricultural University, Guangzhou, P.R. China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Cheng
authors.forename: Isaac
authors.initials: I
authors.lastname: Eliaz
authors.forename: Junfang
authors.initials: J
authors.lastname: Lin
authors.forename: Anita
authors.initials: A
authors.lastname: Thyagarajan-Sahu
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives / Q000494:pharmacology; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000166:cytology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D055441:Poria / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C585138:dehydropachymic acid; D007810:Lanosterol; C476268:polyporenic acid C; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C102487:pachymic acid