ReferenceID 1756
Moscatilin Inhibits Metastatic Behavior of Human Hepatocellular Carcinoma Cells: A Crucial Role of uPA Suppression via Akt/NF-κB-Dependent Pathway
Int J Mol Sci
Hepatocellular carcinoma (HCC) frequently shows early invasion into blood vessels as well as intrahepatic metastasis. Innovations of novel small-molecule agents to block HCC invasion and subsequent metastasis are urgentl
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- Reference Id
- 1756
- Evidence Id
- 18346
- Core Evidence Id
- 18346
- Source Reference Id
- 3486
- Herb2 Reference Id
- HBREF004283
- Subject Paper Key
- HBIN023302_33805784
- Pubmed Id
- 33805784
- Doi
- 10.3390/ijms22062930
- Paper Title
- Moscatilin Inhibits Metastatic Behavior of Human Hepatocellular Carcinoma Cells: A Crucial Role of uPA Suppression via Akt/NF-κB-Dependent Pathway
- Paper Abstract
- Hepatocellular carcinoma (HCC) frequently shows early invasion into blood vessels as well as intrahepatic metastasis. Innovations of novel small-molecule agents to block HCC invasion and subsequent metastasis are urgently needed. Moscatilin is a bibenzyl derivative extracted from the stems of a traditional Chinese medicine, orchid Dendrobium loddigesii. Although moscatilin has been reported to suppress tumor angiogenesis and growth, the anti-metastatic property of moscatilin has not been elucidated. The present results revealed that moscatilin inhibited metastatic behavior of HCC cells without cytotoxic fashion in highly invasive human HCC cell lines. Furthermore, moscatilin significantly suppressed the activity of urokinase plasminogen activator (uPA), but not matrix metalloproteinase (MMP)-2 and MMP-9. Interestingly, moscatilin-suppressed uPA activity was through down-regulation the protein level of uPA, and did not impair the uPA receptor and uPA inhibitory molecule (PAI-1) expressions. Meanwhile, the mRNA expression of uPA was inhibited via moscatilin in a concentration-dependent manner. In addition, the expression of phosphorylated Akt, rather than ERK1/2, was inhibited by moscatilin treatment. The expression of phosphor-IkappaBalpha, and -p65, as well as kappaB-luciferase activity were also repressed after moscatilin treatment. Transfection of constitutively active Akt (Myr-Akt) obviously restored the moscatilin-inhibited the activation of NF-kappaB and uPA, and cancer invasion in HCC cells. Taken together, these results suggest that moscatilin impedes HCC invasion and uPA expression through the Akt/NF-kappaB signaling pathway. Moscatilin might serve as a potential anti-metastatic agent against the disease progression of human HCC.
- Journal
- Int J Mol Sci
- Publish Year
- 2021
- Experiment Subject
- human; highly invasive human hcc cell lines
- Experiment Type
- Cell Experiment
- Phenotype Related
- Tumor; Cancer; Intrahepatic Metastasis; Hepatocellular Carcinoma
- Paper Title Cn
- Paper Title En
- Moscatilin Inhibits Metastatic Behavior of Human Hepatocellular Carcinoma Cells: A Crucial Role of uPA Suppression via Akt/NF-κB-Dependent Pathway
- Bilingual Status
- semi_complete