Sousa Ana Carolina Prado, Oliveira Carlo José Freire, Szabó Matias Pablo Juan, Silva Marcelo José Barbosa
Laboratory of Tumor Biomarkers and Osteoimmunology, Institute of Biomedical Sciences, Federal University of Uberlândia, MG, Brazil; Ixodologia Laboratory, Faculty of Veterinary Medicine, Federal University of Uberlândia, MG, Brazil.
Institute of Natural and Biological Sciences, Laboratory of Immunology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
Toxicon. 2018 Jun 15;148:165-171. doi: 10.1016/j.toxicon.2018.04.024. Epub 2018 Apr 27.
Cancer is one of the most troubling diseases and is becoming increasingly common. Breast cancer has a high cure rate when diagnosed early, but when diagnosed late, treatment is frequently painful, devastating and unsuccessful. The search for new treatments that are more effective and less harmful has led to several substances and biomolecules from plants and animals with potential anti-tumor activity. Within this context, ticks have emerged as an excellent source of new molecules with a wide array of therapeutic properties. Various molecules in tick saliva have immunomodulatory, anticoagulant, anti-inflammatory and anti-tumor effects across different tumor cell lines. Our study evaluates the effect of saliva from three widespread and important tick species in Brazil (Amblyomma sculptum, Amblyomma parvum and Rhipicephalus sanguineus) on MCF-7, MDA-MB-231 breast cancer cell lines and on the non-neoplastic MCF-10A cell line. We found that tick saliva from all three tick species showed cytotoxicity to tumor cells (MCF-7, MDA-MB-231) but not to the non-tumor cells (MCF-10A). Morphological changes on the surface of MCF-7 and MDA-MB-231 tumor cells did not occur on the MCF-10A cells. We also demonstrated that tumor cells die by apoptosis induced by caspase-3 and caspase 7 activity, suggesting that intrinsic pathway apoptosis may be triggered by tick saliva. These changes were not observed in MCF10A cells, which remained broadly unchanged even after exposure to diverse types of saliva. These results suggest that tick saliva from these tick species is a source of molecules, or biomolecules, useful for the potential source for the development of new breast cancer drugs.
癌症是最令人困扰的疾病之一，且日益普遍。乳腺癌若早期诊断，治愈率较高，但若晚期诊断，治疗往往痛苦、具有毁灭性且不成功。对更有效且危害更小的新治疗方法的探索，已促使人们从植物和动物中寻找具有潜在抗肿瘤活性的多种物质和生物分子。在此背景下，蜱已成为具有广泛治疗特性的新分子的优质来源。蜱唾液中的各种分子对不同肿瘤细胞系具有免疫调节、抗凝、抗炎和抗肿瘤作用。我们的研究评估了巴西三种广泛且重要的蜱种（刻点钝缘蜱、微小钝缘蜱和血红扇头蜱）的唾液对MCF-7、MDA-MB-231乳腺癌细胞系以及非肿瘤性MCF-10A细胞系的影响。我们发现，这三种蜱种的唾液对肿瘤细胞（MCF-7、MDA-MB-231）均表现出细胞毒性，但对非肿瘤细胞（MCF-10A）无毒性。MCF-7和MDA-MB-231肿瘤细胞表面出现形态变化，而MCF-10A细胞未出现。我们还证明，肿瘤细胞因半胱天冬酶-3和半胱天冬酶7的活性诱导而凋亡，这表明蜱唾液可能触发了内源性凋亡途径。在MCF10A细胞中未观察到这些变化，即使暴露于不同类型的唾液后，它们也基本保持不变。这些结果表明，这些蜱种的蜱唾液是分子或生物分子的来源，可能是开发新型乳腺癌药物的潜在来源。
