Antimetastatic effect of nobiletin through the down-regulation of CXC chemokine receptor type 4 and matrix metallopeptidase-9
| Autor: | Il-Moo Chang, Dongwoo Nam, Sung-Hoon Kim, Seung-Hoon Choi, Junhee Lee, Kwang Seok Ahn, Seung Ho Baek, Sung-Moo Kim, Bum Sang Shim, Kyoo Seok Ahn |
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| Rok vydání: | 2012 |
| Předmět: |
Receptors
CXCR4 Blotting Western Down-Regulation Pharmaceutical Science Breast Neoplasms Electrophoretic Mobility Shift Assay Context (language use) Nobiletin Inhibitory Concentration 50 chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Electrophoretic mobility shift assay RNA Messenger CXC chemokine receptors Neoplasm Metastasis Pharmacology Reverse Transcriptase Polymerase Chain Reaction Kinase Chemistry NF-kappa B food and beverages General Medicine Flavones Antineoplastic Agents Phytogenic Gene Expression Regulation Neoplastic Blot Reverse transcription polymerase chain reaction Matrix Metalloproteinase 9 Complementary and alternative medicine Biochemistry Cancer cell Cancer research Molecular Medicine Mitogen-Activated Protein Kinases |
| Zdroj: | Pharmaceutical Biology. 50:1210-1218 |
| ISSN: | 1744-5116 1388-0209 |
| DOI: | 10.3109/13880209.2012.664151 |
| Popis: | Nobiletin is one of the citrus bioflavonoids and can be found in citrus fruits such as lemons, oranges, tangerines, and grapefruits. The most studied properties of nobiletin are its anti-inflammatory and anticancer activities.The exact mechanisms of how nobiletin inhibits tumor metastasis and invasion are still not fully understood. In this study, we screened various natural compounds to down-modulate the CXC chemokine receptor-4 (CXCR4) and matrix metallopeptidase-9 (MMP-9).The effect of nobiletin on the constitutive expressions of CXCR4 and MMP-9, MMP-9 enzymatic activity, associated nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation, and tumor cell invasion in human breast cancer cells was investigated. CXCR4 and MMP-9 expression were evaluated via reverse transcription polymerase chain reaction (RT-PCR) and western blotting. NF-κB activation was also evaluated by electrophoretic mobility shift assay (EMSA). In addition, the antimetastatic effects of nobiletin were determined by gelatin zymography and invasion assay.Nobiletin down-regulated both the constitutive expressions of CXCR4 and MMP-9 in human breast cancer cells with IC(50) values of 32 and 24 µM, respectively. Nobiletin also suppressed MMP-9 enzymatic activity and tumor cell invasion under noncytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the nobiletin-induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the down-regulation of CXCR4 and MMP-9 were at the transcriptional level, as indicated by the down-regulation of mRNA expression and the suppression of the constitutive NF-κB and MAPKs activation.Our results indicate, for the first time, that nobiletin is a novel blocker of CXCR4 and MMP-9 expressions and thus has the potential to suppress metastasis of breast cancer. |
| Databáze: | OpenAIRE |
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