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Characterization of the antitumor potential of solamargin against human Glioblastoma

Grant number: 22/00806-4
Support Opportunities:Regular Research Grants
Duration: February 01, 2023 - January 31, 2025
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Principal Investigator:Denise Crispim Tavares Barbosa
Grantee:Denise Crispim Tavares Barbosa
Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil

Abstract

The complexity of the tumor microenvironment, associated with genetic heterogeneity and the invasive nature of glioblastoma (GB), make it one of the most resistant neoplasms to antineoplastic therapy. Currently, surgery, with extensive tumor resection, combined with radiotherapy and chemotherapy, is the standard of majority intervention in the treatment of GB. However, such therapeutic strategies have limited impact on the patient's life prognosis, causing an invariably fatal clinical course. In the search for new molecules for the treatment of GB, as well as in the reduction of side effects of existing treatments, products of natural origin are highlighted in cancer chemotherapy, and can be used in treatments alone or in combination with other anticancer drugs. . In this sense, the steroidal glycoalkaloid solamargine (SM) has cytotoxic, antitumor and chemosensitizing activities supported by the literature. In view of the above, the present study aims to evaluate the antitumor activity of MS against GB. Therefore, assays will be conducted to analyze the influence of SM on proliferation, clonogenicity, morphology, apoptosis, cycle, migration and cell invasion in human glioblastoma lines (U-87MG, U-251MG, T98G and KNS-42), from isolated form and combined with the chemotherapy drug temozolomide. Additionally, in vivo studies will be conducted with the aim of evaluating the antitumor activity of SM in a murine GB model using the U-87MG cell line, whose parameters of antitumor activity (volume, mass, histology and tumor control index) and toxicological (survival of animals, tissue and body mass, water consumption, biochemical dosages and genotoxicity) will be analyzed. In order to better understand the mechanisms of action of SM in GB, evaluations of gene expression in apoptotic signaling and cell proliferation pathways will be performed. This investigation may provide perspectives in the identification of new therapeutic strategies for the treatment of GB. (AU)

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