Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Abstract

Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell proteomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell lines were treated with sub-toxic doses at either 0.63 μg/mL (low) or 2.5 μg/mL (high) of B. jararaca venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). More than 1000 proteins were identified and evaluated from each cell line treated with either the low or high dose of the snake venom. Protein profiling upon venom treatment showed differential expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel biochemical strategy to identify therapeutic targets against cancer cell growth and survival.

Development of a novel prognostic signature based on single‐cell combined bulk RNA analysis in breast cancer

“…GLUL, linked to tumor growth stimulation in BC, 42 was also identified as a responder in BC metabolism under hypoxic conditions in 2019 43 . GSTM3, within the GSTM4–GSTM2–GSTM1–GSTM5–GSTM3 cluster, has been associated with cancer susceptibility since 2010, 44 with subsequent studies affirming its role in BC 45–47 . GSK‐3 can modulate the sensitivity of MIA‐PaCa‐2 pancreatic and MCF‐7 BC cells to chemotherapy agents, targeted treatments and nutraceuticals, according to 2021 study, 48 and a connection between MIA and BC prevalence and progression was reported in 2014 49 .…”

“…43 GSTM3, within the GSTM4-GSTM2-GSTM1-GSTM5-GSTM3 cluster, has been associated with cancer susceptibility since 2010, 44 with subsequent studies affirming its role in BC. [45][46][47] GSK-3 can modulate the sensitivity of MIA-PaCa-2 pancreatic and MCF-7 BC cells to chemotherapy agents, targeted treatments and nutraceuticals, according to 2021 study, 48 and a connection between MIA and BC prevalence and progression was reported in 2014. 49 ACTL8 has been consistently linked with poor BC prognosis in several studies.…”

Prospecção Tecnológica: potencial terapêutico de moléculas presentes no veneno de serpentes do gênero Bothrops sp., com ênfase na espécie Bothrops jararaca

“…Enfim, há também atividades envolvendo o uso do veneno de Bothrops jararaca como modulador de alvos protéicos ligados às células cancerígenas, em que o veneno em si ou alguns de seus componentes demonstraram a capacidade de inibir a proliferação de células cancerígenas, bem como ter o potencial de ser utilizado para a detecção de novos alvos para o tratamento de câncer (Kisaki et al, 2021). Em adição, foram relatados possíveis protótipos de antimicrobianos para o desenvolvimento de novos antibióticos contra bactérias resistentes aos atuais medicamentos (Ferreira et al, 2011).…”

“…Posto isso, é notável a ausência de patentes direcionadas ao desenvolvimento de agentes antimicrobianos, antivirais, antiparasitários e até mesmo anticancerígenos, uma vez que estudos já relataram esse potencial (Muller et al, 2012;Ferreira et al, 2011;Adade et al, 2014;Badari et al, 2021;Kisaki et al, 2021). O atual cenário revela uma ênfase no desenvolvimento de terapias para tratar alteração no sistema de coagulação, acrescido de uma tímida iniciativa para descobrir novos biomarcadores para a detecção de diversas doenças.…”

Celebrating 120 Years of Butantan Institute Contributions for Toxinology

“…We selected 19 original articles and 4 reviews approaching several points of Toxinology. The venom of snakes was approached in different aspects as the structural and functional variability in the composition of venoms from individual snakes [1], the mechanisms of action of whole venoms [2,3], the mechanisms of action of individual components as crotoxin [4], phospholipases A2 [5], metalloproteinases [6][7][8], and the oral immunity induced by whole venoms and their components [9]. Venoms from other animals are also reported; the venoms of centipedes [10], scorpions [11,12], fishes [13,14], and caterpillars [15], including microbial toxins [16].…”