Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 33, Issue -, Pages 63-72Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2016.03.004
Keywords
Caffeine; Glioma; Cathepsin B; MAPK; Invasion
Funding
- Ministry of Science and Technology, Taiwan [MOST 103-2320-B016-003-MY3]
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Glioblastoma has aggressive proliferative and invasive properties. We investigated the effect of caffeine on the invasion and the anti-cancer effect in human glioblastomas. Caffeine reduced the invasion in U-87MG, GBM8401 and LN229 cells. Caffeine decreased mRNA, protein expression, and activity of cathepsin B. Besides, mRNA and protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was upregulated by caffeine treatment, whereas matrix metalloproteinase-2 (MMP-2) was downregulated. The expression of Ki67, p-p38, phospforylated extracellular regulated protein kinases (p-ERK), and membranous integrin beta 1 and beta 3 was decreased by caffeine. The Rho-associated protein kinase (ROCK) inhibitor, Y27632, blocked the caffeine-mediated reduction of cathepsin B, phosphorylated focal adhesion kinase (p-FAK), and p-ERK, and invasion. Moreover, caffeine decreased the tumor size, cathepsin B and Ki67 expression in animal model. Caffeine reduced the invasion of glioma cells through ROCK-cathepsin B/FAK/ERK signaling pathway and tumor growth in orthotopic xenograft animal model, supporting the anti-cancer potential in glioma therapy. (C) 2016 Elsevier Inc. All rights reserved.
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