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: Shujie Cheng, Isaac Eliaz, Junfang Lin, Anita Thyagarajan-Sahu, Daniel Sliva
• Journal: International journal of oncology (Int J Oncol) Vol. 42 Issue 6 Pg. 1869-74 (Jun 2013) ISSN: 1791-2423 [Electronic] Greece
• PMID: 23588713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Triterpenes
• dehydropachymic acid
• Lanosterol
• polyporenic acid C
• MMP7 protein, human
• Matrix Metalloproteinase 7
• pachymic acid

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Down-Regulation (drug effects)
• Gene Silencing
• Humans
• Lanosterol (analogs & derivatives, pharmacology)
• Matrix Metalloproteinase 7 (genetics, metabolism)
• Pancreatic Ducts (cytology, pathology)
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Poria (chemistry)
• Triterpenes (isolation & purification, pharmacology)