响尾蛇毒素在乳腺三阴性肿瘤中的抗肿瘤和抗增殖作用。

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
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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引用次数: 0

摘要

三阴性乳腺癌约占乳腺癌病例的15%。是一种预后不良的乳腺癌,因为它有很高的复发率、转移率和死亡率,并且对治疗有抗药性。推荐的治疗方法是使用蒽环类药物与紫杉烷,然而,这些药物有几个副作用。因此,需要新的治疗方法。响尾蛇毒素是南美洲响尾蛇Crotalus durissus terrificus毒液中的主要毒素,是一种具有磷脂酶A2 (PLA2)活性的强效β-神经毒素。它对几种类型的肿瘤细胞表现出优先的细胞毒性活性,对表达高水平表皮生长因子受体的细胞系具有最大的细胞毒性。考虑到这一点,在本研究中,我们在代表三阴性乳腺癌的细胞系(MDA-MB-231肿瘤细胞)中评估了触发响尾蛇毒素抗肿瘤作用的生物学机制。结果表明,响尾蛇毒素具有抗凋亡、抗自噬和促坏死作用。促坏死作用通过细胞凋亡逃避、自噬抑制和DNA损伤机制发生。因此,本研究对进一步了解响尾蛇毒素在三阴性乳腺癌中的作用及其机制具有重要的里程碑意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Antitumor and antiproliferative potential of crotoxin in triple negative breast tumors

Antitumor and antiproliferative potential of crotoxin in triple negative breast tumors
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
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.
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