HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Maslinic acid inhibits the metastatic capacity of DU145 human prostate cancer cells: possible mediation via hypoxia-inducible factor-1α signalling.

Abstract
Maslinic acid is found in various natural sources, most notably in pomace olive oil, and exerts pro-apoptotic activities in various cancer cells in vitro. In the present study, DU145 human prostate cancer cells were cultured with 0-25 μm-maslinic acid to examine the effects of maslinic acid on the metastatic capacity of prostate cancer cells. Maslinic acid significantly (P <0.05) inhibited the basal and epidermal growth factor (EGF)-induced migration (27-64 %), invasion (23-60 %) and adhesion (8-40 %) of DU145 cells. Maslinic acid significantly (P <0·05) down-regulated both basal and EGF-stimulated secretion of matrix metalloproteinase (MMP)-9 (25-67 %), MMP-2 (50-86 %), urokinase-type plasminogen activator (uPA, about 100 %), vascular endothelial growth factor (VEGF, 98-100 %) and tissue inhibitors of metalloproteinases (TIMP)-1, as well as expression of uPA receptor (uPAR), intercellular adhesion molecules (22-33 %), vascular cell adhesion molecules (23-46 %) and E-cadherin, whereas it increased TIMP-2 secretion. Maslinic acid dramatically reduced the levels of hypoxia-inducible factor-1α (HIF-1α) protein and mRNA; the reduction was accompanied by reduced stability, nuclear levels and transcriptional activity of HIF-1α. The levels of phospho-Akt and phospho-extracellular signal-related kinase (ERK) were reduced in cells treated with maslinic acid, and the phosphoinositide 3-kinase inhibitor LY294002 and the mitogen-activated protein kinase kinase inhibitor PD98059 reduced HIF-1α levels and VEGF secretion. The results show that maslinic acid markedly inhibited the migration, invasion and adhesion of DU145 prostate cancer cells. Suppressing HIF-1α activation by inhibiting Akt and ERK activation may be part of the mechanism by which maslinic acid inhibited uPAR, E-cadherin, VEGF and MMP expression in DU145 cells.
AuthorsSo Young Park, Chu Won Nho, Dae Young Kwon, Young-Hee Kang, Ki Won Lee, Jung Han Yoon Park
JournalThe British journal of nutrition (Br J Nutr) Vol. 109 Issue 2 Pg. 210-22 (Jan 28 2013) ISSN: 1475-2662 [Electronic] England
PMID22716951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neoplasm Proteins
  • RNA, Messenger
  • Triterpenes
  • maslinic acid
Topics
  • Angiogenesis Inhibitors (pharmacology)
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Cell Adhesion (drug effects)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Cell Nucleus (drug effects)
  • Down-Regulation (drug effects)
  • Genes, Reporter (drug effects)
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, genetics, metabolism)
  • Male
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism, secretion)
  • Prostatic Neoplasms (drug therapy, metabolism, pathology, secretion)
  • Protein Stability (drug effects)
  • RNA, Messenger (metabolism)
  • Signal Transduction (drug effects)
  • Triterpenes (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: