A novel protein from the serum of Python sebae, structurally homologous to γ-phospholipase A2 inhibitor, displays antitumor activity.

DONNINI, S, FINETTI, F, FRANCESE, Simona, BOSCARO, F, DANI, F, MASET, F, FRASSON, R, PLAMIERI, M, PAZZAGLI, M, DE FILIPPIS, V, GARACI, E and ZICHE, M (2011). A novel protein from the serum of Python sebae, structurally homologous to γ-phospholipase A2 inhibitor, displays antitumor activity. Biochemical Journal, 440 (2), 251-262.

Full text not available from this repository.
Link to published version:: 10.1042/BJ20100739

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 PLA2 (phospholipase A2) inhibitor] from Python reticulatus}, existing as a homohexamer. More importantly, although PIP inhibits the hydrolytic activity of PLA2, the anti-PLA2 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.

Item Type: Article
Research Institute, Centre or Group: Biomedical Research Centre
Identification Number: 10.1042/BJ20100739
Depositing User: Rebecca Jones
Date Deposited: 08 Feb 2012 16:48
Last Modified: 08 Feb 2012 16:48
URI: http://shura.shu.ac.uk/id/eprint/4389

Actions (login required)

View Item

Downloads

Downloads per month over past year

View more statistics