Maslinic acid inhibits the metastatic capacity of DU145 human prostate cancer cells: possible mediation via hypoxia-inducible factor-1 alpha signalling
- Authors
- Park, So Young; Nho, Chu Won; Kwon, Dae Young; Kang, Young-Hee; Lee, Ki Won; Park, Jung Han Yoon
- Issue Date
- 2013-01-28
- Publisher
- CAMBRIDGE UNIV PRESS
- Citation
- BRITISH JOURNAL OF NUTRITION, v.109, no.2, pp.210 - 222
- 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 mM-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-1 alpha (HIF-1 alpha) protein and mRNA; the reduction was accompanied by reduced stability, nuclear levels and transcriptional activity of HIF-1 alpha. 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-1 alpha levels and VEGF secretion. The results show that maslinic acid markedly inhibited the migration, invasion and adhesion of DU145 prostate cancer cells. Suppressing HIF-1 alpha 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.
- Keywords
- MATRIX METALLOPROTEINASES; NATURAL TRITERPENE; FACTOR 1-ALPHA; TUMOR-GROWTH; EXPRESSION; PROLIFERATION; ANGIOGENESIS; PATHWAY; HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA; HIF-1-ALPHA; MATRIX METALLOPROTEINASES; NATURAL TRITERPENE; FACTOR 1-ALPHA; TUMOR-GROWTH; EXPRESSION; PROLIFERATION; ANGIOGENESIS; PATHWAY; HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA; HIF-1-ALPHA; Metastasis; Prostate cancer cells; Hypoxia-inducible factor-1 alpha; Vascular endothelial growth factor; Matrix metalloproteinase
- ISSN
- 0007-1145
- URI
- https://pubs.kist.re.kr/handle/201004/128433
- DOI
- 10.1017/S0007114512000967
- Appears in Collections:
- KIST Article > 2013
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.