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Amazon scorpion toxin kills breast cancer cells

The venom of a common species of Amazonian scorpion may give rise to a potential drug for treating a cancer that is one of the leading causes of death in women.

Researchers at the University of São Paulo's Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP) in Brazil have identified a molecule in the toxin of Brotheas amazonicus that acts against breast cancer cells similarly to a common chemotherapy drug.

Preliminary results of the study, carried out in collaboration with researchers from the National Institute for Amazonian Research (INPA) and the Amazonas State University (UEA), were presented during , which took place from June 10–12 in the capital of the Occitanie region in southern France.

"Through bioprospecting, we were able to identify a molecule in the species of this Amazonian scorpion that is similar to that found in the venoms of other scorpions and that acts against breast cancer cells," Eliane Candiani Arantes, a professor at FCFRP-USP and the project's coordinator, told Agência FAPESP.

Researchers affiliated with the institution are dedicated to cloning and expressing bioactive molecules—such as proteins from rattlesnake and scorpion venom—through projects within the scope of the Center for Translational Science and Development of Biopharmaceuticals (CTS), located at the Center for the Study of Venoms and Venomous Animals (CEVAP) of São Paulo State University (UNESP), in its Botucatu campus.

This work has resulted in the development of a patented CEVAP product called fibrin sealant, a "biological glue" made from serineproteinase extracted from snake venom (such as from Bothrops neuwiedi pauloensis and Crotalus durissus terrificus) and cryoprecipitate rich in fibrinogen extracted from the blood of buffalo, cattle, or sheep.

These components combine in application to form a fibrin network that mimics the natural coagulation and healing processes. The sealant has been studied for use in nerve gluing, treating bone injuries, and restoring movement after spinal cord injuries. It is currently in phase three clinical trials, the final stage of analysis for a new drug before approval.

Recently, researchers cloned and expressed a different rattlesnake serine protease called cholinein-1. This protease has a different amino acid sequence from the gyroxine toxin, which is extracted directly from rattlesnake venom and used in the production of fibrin sealant.

"Our idea now is to obtain this serine protease through heterologous expression [in a fragment or complete gene from a host organism that doesn't have it naturally] in Pichia pastoris," said Arantes.

Through heterologous expression in this yeast isolated in France in 1950, the researchers also intend to obtain an endothelial growth factor called CdtVEGF, which was identified in the rattlesnake species Crotalus durissus terrificus.

"This growth factor favors the formation of new vessels. If we combine it with colinein-1, we can create an improved fibrin sealant compared to the one being developed at CEVAP, with the possibility of expanding the industrial scale, since it can be obtained through heterologous expression," she said.

Through heterologous expression, the researchers also identified two neurotoxins with immunosuppressive action in scorpions. In partnership with colleagues from INPA and UEA, they discovered a bioactive molecule called BamazScplp1 in the venom of the Brotheas amazonicus scorpion that has potential anti-tumor properties.

Test results of the peptide on breast cancer cells revealed a response comparable to that of paclitaxel, a chemotherapy drug commonly used to treat the disease. The peptide induces cell death mainly through necrosis, an action similar to that of molecules identified in other scorpion species.

"We also intend to obtain these molecules through heterologous expression," said Arantes.