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

56 Scopus citations

Abstract

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
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

Fingerprint Dive into the research topics of 'Role of the cystathionine γ lyase/hydrogen sulfide pathway in human melanoma progression'. Together they form a unique fingerprint.

Cite this