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Lycorine inhibits melanoma cell migration and metastasis mainly through reducing intracellular levels of β-catenin and matrix metallopeptidase 9
- Source :
- Journal of cellular physiology. 234(7)
- Publication Year :
- 2018
-
Abstract
- Metastatic melanoma accounts for 60% of death for skin cancer. Although great efforts have been made to treat the disease, effective drugs against metastatic melanoma still lack at the clinical setting. In the current study, we found that lycorine, a small molecule of isoquinoline alkaloid, significantly suppressed melanoma cell migration and invasion in vitro, and decreased the metastasis of melanoma cells to lung tissues in tumor-bearing mice, resulting in significant prolongation of the survival of the mice without obvious toxicity. Molecular mechanistic studies revealed that lycorine significantly reduced intracellular levels of β-catenin protein through degradation of the protein via the ubiquitin-proteasome pathway, and decreased the expression of β-catenin downstream prometastatic matrix metallopeptidase 9 and Axin2 genes. Collectively, our findings support the notion that targeting the oncogenic β-catenin by lycorine is a new option to inhibit melanoma cell metastasis, providing a good drug candidate potential for development novel therapeutics against metastatic melanoma.
- Subjects :
- 0301 basic medicine
Physiology
Clinical Biochemistry
Cell
Apoptosis
MMP9
Metastasis
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Axin Protein
Cell Movement
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Metastasis
Melanoma
beta Catenin
Cell Proliferation
Chemistry
Cell migration
Cell Biology
medicine.disease
Lycorine
Xenograft Model Antitumor Assays
Phenanthridines
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
Matrix Metalloproteinase 9
030220 oncology & carcinogenesis
Catenin
Cancer research
Amaryllidaceae Alkaloids
Intracellular
Signal Transduction
Subjects
Details
- ISSN :
- 10974652
- Volume :
- 234
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of cellular physiology
- Accession number :
- edsair.doi.dedup.....72ca418a770edc4b19db21668a2e8c7b