Antitumor potential of Pllans–II, an acidic Asp49–PLA2 from Porthidium lansbergii lansbergii snake venom on human cervical carcinoma HeLa cells

Abstract

This work shows for the first time the antitumoral and angiostatic potential effects of Pllans–II, an acidic monomeric Asp49–PLA2 from Porthidium lansbergii lansbergii snake venom on HeLa cells. Pllans–II exhibited a predominant dose–dependent cytotoxicity on cervical carcinoma HeLa cells more than human breast cancer MCF7 and MDA–MB–231 cells. Interestingly, Pllans–II showed negligible effect in vitro on normal cells such as MCF 10A, a non–tumorigenic breast epithelial cell and endothelial cells–HUVEC. Besides, Pllans–II induced a significative cell cycle arrest in G1 phase of treated HeLa. Flow Cytometry analysis showed that Pllans–II induced both early and late apoptosis on HeLa cells, verified by the modulation of important genes mediators of apoptosis pathways such as CASP8, BCL2L1, BCL2, BAX, BAD and BIRC5, showing a possible apoptotic cell death triggered through extrinsic pathways. Pllans–II was also able to inhibit cell migration on HeLa cells by interfering with α5 and β1–containing integrins. In addition, Pllans–II inhibited in vitro angiogenesis on endothelial HUVEC cells through VEGF–independent pathway. Our results display that Pllans–II is able to be an anticancer target for the development of a new antitumoral prototype.