Author: Benavides, Jorge ; Mayolo-Deloisa, Karla ; Cossío-Ramírez, Raquel ; Melendez-Martinez, David ; Lozano, Omar ; Rito-Palomares, Marco ; Morales-Martinez, Adriana ; Sierra-Valdez, Francisco

01 May 2024·Toxicon

Effects of crotamine in human prostate cancer cell line

Article

Author: Pucca, Manuela Berto ; Alberghini-Dos-Santos, João Victor ; Bordon, Karla de Castro Figueiredo ; Oliveira, Isadora Sousa de ; Sanchez, Caroline Andolfato ; Antunes, Lusânia Maria Greggi ; Arantes, Eliane Candiani

Our study presents the anticancer potential of crotamine from Crotalus durissus terrificus in human prostate cancer cell line DU-145. Crotamine isolation was conducted through RP-FPLC, its molecular mass analyzed by MALDI-TOF was 4881.4 kDa, and N-terminal sequencing confirmed crotamine identity. Crotamine demonstrated no toxicity and did not inhibit migration in HUVEC cells. Although no cell death occurred in DU-145 cells, crotamine inhibited their migration. Thus, crotamine presented potential to be a prototype of anticancer drug.

01 Nov 2023·International Journal of Pharmaceutics

Evaluation of tumor growth remission in a murine model for subcutaneous solid tumors – Benefits of associating the antitumor agent crotamine with mesoporous nanosilica particles to achieve improved dosing frequency and efficacy

Article

Author: Porta, Lucas C ; Hayashi, Mirian Akemi Furuie ; Sant'Anna, Osvaldo A ; Nani, João V ; Alves, Wendel A ; Anthero, Gabriel Lessa ; Oyadomari, William Yoshio ; Oliveira, Vitor ; Silva, Marcos R de A ; Reid, Paul F

Crotamine is a highly cationic polypeptide first isolated from South American rattlesnake venom, which exhibits affinity for acidic lysosomal vesicles and proliferating cells. This cationic nature is pivotal for its in vitro cytotoxicity and in vivo anticancer actions. This study aimed to enhance the antitumor efficacy of crotamine by associating it with the mesoporous SBA-15 silica, known for its controlled release of various chemical agents, including large proteins. This association aimed to mitigate the toxic effects while amplifying the pharmacological potency of several compounds. Comprehensive characterization, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis, confirmed the successful association of crotamine with the non-toxic SBA-15 nanoparticles. The TEM imaging revealed nanoparticles with a nearly spherical shape and variations in uniformity upon crotamine association. Furthermore, DLS showed a narrow unimodal size distribution, emphasizing the formation of small aggregates. Zeta potential measurements indicated a distinct shift from negative to positive values upon crotamine association, underscoring its effective adsorption onto SBA-15. Intraperitoneal or oral administration of crotamine:SBA-15 in a murine melanoma model suggested the potential to reduce the frequency of crotamine doses without compromising efficacy. Interestingly, while the oral route enhanced the antitumor efficacy of crotamine, pH-dependent release from SBA-15 was observed. Thus, associating crotamine with SBA-15 could reduce the overall required dose to inhibit solid tumor growth, bolstering the prospect of crotamine as a potent anticancer agent.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	IE	Celtic Biotech Ltd.	-

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