Park, So Young Nho, Chu Won Kwon, Dae Young Kang, Young-Hee Lee, Ki Won Park, Jung Han Yoon 2024-01-20T13:03:16Z 2024-01-20T13:03:16Z 2021-09-01 2013-01-28 0007-1145 https://pubs.kist.re.kr/handle/201004/128433 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. English CAMBRIDGE UNIV PRESS MATRIX METALLOPROTEINASES NATURAL TRITERPENE FACTOR 1-ALPHA TUMOR-GROWTH EXPRESSION PROLIFERATION ANGIOGENESIS PATHWAY HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA HIF-1-ALPHA Maslinic acid inhibits the metastatic capacity of DU145 human prostate cancer cells: possible mediation via hypoxia-inducible factor-1 alpha signalling Article 10.1017/S0007114512000967 1 BRITISH JOURNAL OF NUTRITION, v.109, no.2, pp.210 - 222 BRITISH JOURNAL OF NUTRITION 109 2 210 222 scie scopus 000313975800003 2-s2.0-84873045777 Nutrition & Dietetics Nutrition & Dietetics Article 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