Potencial antineoplásico e efeito terapêutico adjuvante da crotoxina extraída do veneno da serpente Crotalus durissus terrificus : revisão sistemática e estudo in vitro em células de carcinoma epidermoide de boca

Abstract

Oral squamous cell carcinoma (OSCC) is the sixth most common neoplasm in the world and represents more than 90% of all malignant tumors of the oral cavity. In individuals affected by OSCC, radiotherapy is an important therapeutic strategy to promote the death of neoplastic cells and to control the progression of the disease. Despite the advances obtained in this treatment modality, there are still cases of radioresistance, which can lead to an unfavorable prognosis. It is crucial to carry out research aimed at developing complementary therapies, aiming to favor the effectiveness of ionizing radiation. The poisons are promising sources for the discovery of new antineoplastic agents. Crotoxin (CrTX), a toxin isolated from the poison of the South American rattlesnake Crotalus durissus terrificus, has some biological activities, which include neurotoxic, immunomodulatory, anti- inflammatory, antimicrobial, analgesic and antineoplastic actions. Given the above, this study encompasses two strands of work. The first aimed to verify the antineoplastic potential of CrTX in different types of cancer, through a systematic review. The objective of the second approach was to evaluate the adjuvant therapeutic effect of CrTX in OSCC cells. The systematic review of the first study involved the search for in vitro and clinical studies related to the proposed objective. The study was registered on the international platform Prospero (CRD42019137665) and followed the search criteria of the PRISMA Platform, using the PubMed, Scopus, Web of Science and EBSCO databases. 71 articles on the proposal were identified. From the analysis of these, adopting inclusion and exclusion criteria, a total of 11 articles were selected as eligible for reading the full text. The results of the systematic review showed that crotoxin promoted antiproliferative action, apoptosis, cell cycle arrest and activation of genes to promote the death of cancerous lines, in in vitro studies. A human study suitable for the review proposal was not identified in the literature. In the second part of this study, in vitro assays of proliferation, cell death, and levels of reactive oxygen species (ROS) were performed. Immortalized cells of OSCC, SCC-9, were treated with CrTX at a concentration of 100 µg/ml for 72 hours, followed by exposure to 2, 4 and 6 Gy of irradiation, in a linear accelerator. The CrTX was able to increase the sensitivity of CEB cells to ionizing radiation, decreasing proliferative activity, increasing cell death and the formation of ROS. The findings of this study demonstrated that the crotoxin enhances the therapeutic effect of ionizing radiation, increasing its therapeutic effect of radiation on OSCC cells. Thus, CrTX exerted an antineoplastic effect on different types of neoplasms and an adjuvant effect to radiation on OSCC cells and can be appointed as a promising therapeutic strategy for future clinical research for the treatment of patients with oral cancer.