Affiliation:
1. Programa de Doutorado em Biotecnologia—Rede Nordeste de Biotecnologia (RENORBIO), Center for Basic and Applied Immunology (NIBA), Federal University of Maranhão, São Luís 65080-805, Maranhão, Brazil
2. Programa de Pós-Graduação em Saúde do Adulto (PPGSAD), Center for Basic and Applied Immunology (NIBA), Federal University of Maranhão, São Luís 65080-805, Maranhão, Brazil
3. Departament of Medicina I, Federal University of Maranhão, Imperatriz 65915-060, Maranhão, Brazil
Abstract
Cervical cancer is caused by a persistent and high-grade infection. It is caused by the Human Papillomavirus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. It is known that L-asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers. Due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions, and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization, and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50 °C, resistance to surfactants and metallic ions, and an increase in enzymatic activity with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from A. niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity, and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.
Funder
Coordenação de Aperfeicoamento de Pessoal de Nível Superior
Reference47 articles.
1. Human papillomavirus and cervical cancer;Okunade;J. Obstet. Gynaecol.,2020
2. Real-time PCR HPV genotyping in fine needle aspirations of metastatic head and neck squamous cell carcinoma: Exposing the limitations of conventional p16 immunostaining;Mansour;Oral Oncol.,2019
3. Oliveira, M.A.A., Mascarenhas, G.M.S., de Sousa Lima, A.A., Carneiro, V.M.S., Silva, C.D.C.M., and Silva, M.V.C.M. (2022). Correlation of genetic factors of hpv 16/18 virus and cervical cancer. Adv. Stud. Health Nat., 3.
4. Acrylamide reduction in potato chips using commercial asparaginase in combination with conventional bleaching;Pedreschi;LWT Food Sci. Technol.,2011
5. Hemocompatible glutaminase free L-asparaginase from marine Bacillus tequilensis PV9W with anticancer potential modulating p53 expression;Shakambari;RSC Adv.,2016