Journal
CLINICAL & EXPERIMENTAL METASTASIS
Volume 31, Issue 8, Pages 897-907Publisher
SPRINGER
DOI: 10.1007/s10585-014-9678-x
Keywords
Capsaicin; Migration; Cholangiocarcinoma; MMP-9; AMPK; SIRT1; NF-kappa B
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Funding
- Priority Research Center Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2009-0094050]
- Basic Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2013R1A1A4A01009559]
- BK-21 Fund
- National Research Foundation of Korea [2013R1A1A4A01009559] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Cholangiocarcinoma is one of the most difficult malignancies to cure. An important prognostic factor is metastasis, which precludes curative surgical resection. Recent evidence shows that capsaicin has an inhibitory effect on cancer cell migration and invasion. Here, we investigated the molecular mechanism of the capsaicin-induced anti-migration and anti-invasion effects on HuCCT1 cholangiocarcinoma cells. Migration and invasion were significantly reduced in response to capsaicin. Capsaicin also inhibited the expression of matrix metalloproteinase-9 (MMP-9). In capsaicin-treated cells, levels of phosphorylated AMPK increased, and this effect was abolished by treatment with the AMPK inhibitor, Compound C. Capsaicin enhanced the expression of SIRT1, which can activate the transcription factor NF-kappa B by deacetylation. This suggests that NF-kappa B is activated by capsaicin via the SIRT1 pathway. In addition, capsaicin-activated AMPK induced the phosphorylation of I kappa B alpha and nuclear localization of NF-kappa B p65. Chromatin immunoprecipitation assays demonstrated that capsaicin reduced MMP-9 transcription by inhibiting NF-kappa B p65 translocation and deacetylation via SIRT1. These findings provide evidence that capsaicin suppresses the migration and invasion of cholangiocarcinoma cells by inhibiting NF-kappa B p65 via the AMPK-SIRT1 and the AMPK-I kappa B alpha signaling pathways, leading to subsequent suppression of MMP-9 expression.
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