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

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
  • 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)

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