Capsaicin suppresses the migration of cholangiocarcinoma cells by down-regulating matrix metalloproteinase-9 expression via the AMPK–NF-κB signaling pathway

Abstract

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-κB by deacetylation. This suggests that NF-κB is activated by capsaicin via the SIRT1 pathway. In addition, capsaicin-activated AMPK induced the phosphorylation of IκBα and nuclear localization of NF-κB p65. Chromatin immunoprecipitation assays demonstrated that capsaicin reduced MMP-9 transcription by inhibiting NF-κB p65 translocation and deacetylation via SIRT1. These findings provide evidence that capsaicin suppresses the migration and invasion of cholangiocarcinoma cells by inhibiting NF-κB p65 via the AMPK-SIRT1 and the AMPK-IκBα signaling pathways, leading to subsequent suppression of MMP-9 expression.

Spices for Prevention and Treatment of Cancers

“…Capsaicin induced anti-migration and anti-invasion effects in cholangiocarcinoma cells through inhibition of NF-κB p65, resulting in subsequent suppression of MMP-9 expression [207]. In another study, proliferation, migration and invasion of human cholangiocarcinoma cells were all effectively inhibited by capsaicin, which was associated with regulating the Hedgehog signaling pathway [208].…”

Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression

“…Both MMP-19 plays a key role in cancer metastasis and spread. Capsaicin suppresses the migration of cholangiocarcinoma cells by downregulating the MMP-9 expression signaling pathway (9). Recently Ma et al (10) illustrated that SUMO-specific protease 1 regulates the proliferation and invasion of pancreatic cancer cells through MMP-9.…”

Activation of AMPK and its Impact on Exercise Capacity

“…Capsaicin, an agonist of the transient receptor potential vanilloid (TRPV) 1, has also been associated with activation of AMPK in cell culture [103][104][105]. Furthermore, it was found to increase exercise endurance, for instance, by regulation of PGC-1a [106], but a direct impact on AMPK activation remains to be demonstrated.…”