Antitumor and antiproliferative potential of crotoxin in triple negative breast tumors

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon Pub Date : 2025-03-20 DOI:10.1016/j.toxicon.2025.108322

De Andrade Camila Marques , Machado Cleni Mara Marzocchi , De Castro Fabíola Attié , Teixeira Natércia , Amaral Cristina , Campos Felipe , Canicoba Nathália Cristina , Torqueti Maria Regina

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Abstract

Triple negative breast carcinoma represents around 15 % of breast cancer cases. Is a type of breast cancer with poor prognosis, because it has a high rate of recurrence, metastasis and death and can be resistant to therapy. The recommended treatment is the use of anthracyclines with taxanes, however, these medications have several side effects. Thus, there is a need for new therapeutic approaches. Crotoxin, the main toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus, is a potent β-neurotoxin that has phospholipase A2 (PLA2) activity. It exhibits preferential cytotoxic activity against several types of tumor cells and is most cytotoxic to cell lines that express high levels of epidermal growth factor receptors. Considering this, in this study, we evaluated the biological mechanisms that trigger the antitumor effects of crotoxin in a cell line representing triple negative breast carcinoma (MDA-MB-231 tumor cells). Results demonstrated that crotoxin had anti-apoptotic, anti-autophagic and pro-necrotic actions. The pro-necrotic effect occurred through mechanisms of apoptosis evasion, autophagy inhibition and DNA damage. Therefore, this study represents an important milestone to better understand the effects and mechanisms of action of crotoxin in triple negative breast cancer.

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来源期刊

Toxicon 医学-毒理学

CiteScore

4.80

自引率

10.70%

发文量

358

审稿时长

68 days

期刊介绍： Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee. Toxicon''s "aims and scope" are to publish: -articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms -papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins -molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins -clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained. -material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems. -articles on the translational application of toxins, for example as drugs and insecticides -epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged. -articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon. -review articles on problems related to toxinology. To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.