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Role of the cystathionine gamma lyase/hydrogen sulfide pathway in human melanoma progression
- Publication Year :
- 2015
-
Abstract
- In humans, two main metabolic enzymes synthesize hydrogen sulfide (H2 S): cystathionine γ lyase (CSE) and cystathionine β synthase (CBS). A third enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), synthesizes H2 S in the presence of the substrate 3-mercaptopyruvate (3-MP). The immunohistochemistry analysis performed on human melanoma samples demonstrated that CSE expression was highest in primary tumors, decreased in the metastatic lesions and was almost silent in non-lymph node metastases. The primary role played by CSE was confirmed by the finding that the overexpression of CSE induced spontaneous apoptosis of human melanoma cells. The same effect was achieved using different H2 S donors, the most active of which was diallyl trisulfide (DATS). The main pro-apoptotic mechanisms involved were suppression of nuclear factor-κB activity and inhibition of AKT and extracellular signal-regulated kinase pathways. A proof of concept was obtained in vivo using a murine melanoma model. In fact, either l-cysteine, the CSE substrate, or DATS inhibited tumor growth in mice. In conclusion, we have determined that the l-cysteine/CSE/H2 S pathway is involved in melanoma progression.
- Subjects :
- Skin Neoplasms
Cystathionine beta-Synthase
Down-Regulation
Sulfurtransferase
Apoptosis
Dermatology
Sulfides
General Biochemistry, Genetics and Molecular Biology
chemistry.chemical_compound
Cell Line, Tumor
parasitic diseases
medicine
Animals
Humans
Gene Silencing
Hydrogen Sulfide
Neoplasm Metastasis
Nevus
Protein kinase B
Melanoma
Cell Proliferation
chemistry.chemical_classification
biology
Chemistry
Kinase
Cystathionine gamma-Lyase
NF-kappa B
Cell Cycle Checkpoints
medicine.disease
Cystathionine beta synthase
Allyl Compounds
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Enzyme
Diallyl trisulfide
Oncology
Biochemistry
Sulfurtransferases
Disease Progression
Cancer research
biology.protein
Female
hydrogen sulphide
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....df4a0e4d9f2fd59ff6001498ee609b34