Role of the cystathionine γ lyase/hydrogen sulfide pathway in human melanoma progression

Elisabetta Panza, Paola De Cicco, Chiara Armogida, Giosuè Scognamiglio, Vincenzo Gigantino, Gerardo Botti, Domenico Germano, Maria Napolitano, Andreas Papapetropoulos, Mariarosaria Bucci, Giuseppe Cirino, Angela Ianaro

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


In humans, two main metabolic enzymes synthesize hydrogen sulfide (H2S): cystathionine γ lyase (CSE) and cystathionine β synthase (CBS). A third enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), synthesizes H2S 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 H2S 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/H2S pathway is involved in melanoma progression.

Original languageEnglish (US)
Pages (from-to)61-72
Number of pages12
JournalPigment Cell and Melanoma Research
Issue number1
StatePublished - Jan 1 2015
Externally publishedYes


  • Apoptosis
  • Cystathionine γ lyase
  • Hydrogen sulfide
  • Melanoma
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Oncology
  • General Biochemistry, Genetics and Molecular Biology
  • Dermatology


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