Exploring the Safety of Pllans-II and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy.

The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2 "Pllans-II," isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer.

Proteomic and functional analyses of Lachesis acrochorda snake venom from the Valle del Cauca Department of Colombia.

Lachesis acrochorda envenomation has a lethality rate of approximately 90%. Despite its high lethality, little is known about its local and systemic effects and its relationship with its protein content. Thus, to increase knowledge of L. acrochorda snake venom from the Southwestern ecoregion of Colombia, we developed a proteomic analysis using a "bottom-up shotgun proteomic profiling" approach. Besides, we evaluated toxinological properties and compared the effects with the Bothrops asper snake venom activities. The RP-HPLC profile showed similarities with the L. acrochorda snake venom from the Northwestern ecoregion of Colombia. However, the results displayed differences in the protein families identified, probably due to the proteomic identification strategy. The in vitro and in vivo tests showed a L. acrochorda snake venom with Phospholipase A2 and metalloproteinase activities related to myotoxic, edematic, and hemorrhagic effects. Nevertheless, the L. acrochorda snake venom displayed a low lethality despite a large amount of inoculated venom. This investigation's results will help us improve the knowledge about the relationship between the clinical manifestations of L. acrochorda envenomation and the venom protein content.