Decursinol angelate blocks transmigration and inflammatory activation of cancer cells through inhibition of PI3K, ERK and NF-kappaB activation.
Inflammation is known to be closely associated with the development of cancer. Decursinol angelate (DA), a coumarin compound isolated from Angelica gigas and related compounds have been shown to possess potent anti-inflammatory activities. However, little is known about their effects on the inflammatory processes associated with cancer. In this study, the anti-inflammatory effect of DA was evaluated in cancer cell lines with respect to cellular invasion through the extracellular matrix (ECM) and the expression of pro-inflammatory mediators such as cytokine, cell adhesion molecules and matrix metalloproteinase (MMP)-9. DA inhibited the invasion of fibrosarcoma cell line, HT1080 and breast cancer cell line, MDA-MB-231 in the Matrigel invasion assay. DA-mediated suppression of cancer cell invasion was accomplished by suppression of PI3K activity known to be associated with cytoskeletal rearrangement related to cellular migration. DA also suppressed the adhesion of cancer cells to ECM mediated by down-regulation of beta(1)-integrin expression levels. Furthermore, DA inhibited the expression of pro-inflammatory cytokines and MMP-9 through suppression of PI3K, ERK and NF-kappaB activation. These results demonstrate that DA suppresses invasion and inflammatory activation of cancer cells through modulation of PI3K/AKT, ERK and NF-kappaB. These anti-inflammatory activities of DA may contribute to its anti-cancer activity.
Kim
Won-Jung
WJ
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
Lee
Min-Young
MY
Kim
Jung-Hee
JH
Suk
Kyoungho
K
Lee
Won-Ha
WH
D029969:Angelica / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002087:Butyrates / Q000302:isolation & purification / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017931:DNA Primers; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology; D005434:Flow Cytometry; D005780:Gelatin / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D001578:Benzopyrans; D002087:Butyrates; D017931:DNA Primers; D016328:NF-kappa B; D005780:Gelatin; C101278:decursin; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9