A novel protein from the serum of Python sebae, structurally homologous with type-γ phospholipase A 2 inhibitor, displays antitumour activity

Sandra Donnini, Federica Finetti, Simona Francese, Francesca Boscaro, Francesca R. Dani, Fabio Maset, Roberta Frasson, Michele Palmieri, Mario Pazzagli, Vincenzo De Filippis, Enrico Garaci, Marina Ziche

Research output: Contribution to journalArticlepeer-review

Abstract

Cytotoxic and antitumour factors have been documented in the venom of snakes, although little information is available on the identification of cytotoxic products in snake serum. In the present study, we purified and characterized a new cytotoxic factor from serum of the non-venomous African rock python (Python sebae), endowed with antitumour activity. PSS (P. sebae serum) exerted a cytotoxic activity and reduced dose-dependently the viability of several different tumour cell lines. In a model of human squamous cell carcinoma xenograft (A431), subcutaneous injection of PSS in proximity of the tumour mass reduced the tumour volume by 20%. Fractionation of PSS by ion-exchange chromatography yielded an active protein fraction, F5, which significantly reduced tumour cell viability in vitro and, strikingly, tumour growth in vivo. F5 is composed of P1 (peak 1) and P2 subunits interacting in a 1:1 stoichiometric ratio to form a heterotetramer in equilibrium with a hexameric form, which retained biological activity only when assembled. The two peptides share sequence similarity with PIP {PLI-γ [type-γ PLA 2 (phospholipase A 2) inhibitor] from Python reticulatus}, existing as a homohexamer. More importantly, although PIP inhibits the hydrolytic activity of PLA 2, the anti-PLA 2 function of F5 is negligible. Using high-resolution MS, we covered 87 and 97% of the sequences of P1 and P2 respectively. In conclusion, in the present study we have identified and thoroughly characterized a novel protein displaying high sequence similarity to PLI-γ and possessing remarkable cytotoxic and antitumour effects that can be exploited for potential pharmacological applications.

Original languageEnglish
Pages (from-to)251-262
Number of pages12
JournalBiochemical Journal
Volume440
Issue number2
DOIs
Publication statusPublished - Dec 1 2011

Keywords

  • Antitumour activity
  • Apoptosis
  • Python sebae
  • Snake serum
  • Type-γ phospholipase inhibitor (pliγ)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'A novel protein from the serum of Python sebae, structurally homologous with type-γ phospholipase A 2 inhibitor, displays antitumour activity'. Together they form a unique fingerprint.

Cite this