Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthusspp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma

Author(s)

Izumi, Clarice ^{[1, 2]} ; Laure, Helen Julie ^{[1, 2]} ; Barbosa, Nayara Goncalves ^{[1, 2]} ; Hassibe Thome, Carolina ^[3] ; Aguiar Ferreira, Germano ^[3] ; Paulo Barreto Sousa, Joao ^[4] ; Peporine Lopes, Norberto ^[4] ; Cesar Rosa, Jose ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Dept Cell & Mol Biol & Pathogen Bioagents, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Prot Chem Ctr, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14040900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Nucleo Pesquisas Prod Nat Sintet, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 13 JUL 2020.
• Web of Science Citations: 1

Abstract

Gliomas are responsible for more than 60% of all primary brain tumors. Glioblastoma multiforme (GBM), a grade IV tumor (WHO), is one of the most frequent and malignant gliomas. Despite two decades of advances in the discovery of new markers for GBM, the chemotherapy of choice falls to temozolomide after surgery and radiotherapy, which are not enough to increase the survival of patients to more than 15 months. It is urgent to discover new anti-glioma compounds. Many compounds derived from natural products have been used in the development of anti-tumor drugs. In this work, we have screened six low molecular weight sesquiterpene lactones, isolated fromEremanthusspp., and studied their function as anti-proliferative agents against GBM strains. We demonstrated that two of them, goyazensolide and lychnofolide, were effective in reducing cell viability, preventing the formation of anchorage-dependent colony and were able to pass through a mimetic blood-brain barrier making them candidates for glioma therapy, being more potent than temozolomide, according to in vitro assays for the cell lines tested. Proteomic analysis revealed a number of altered proteins involved in glycolytic metabolism and cellular catabolism. (AU)

• FAPESP's process: 16/10632-2 - Functional proteomics: mechanisms of action of new drugs, cellular stress and the role of Unfold Protein Response (UPR ) of the endoplasmic reticulum proteins in glioblastoma cell lines.
• Grantee: José César Rosa
• Support Opportunities: Regular Research Grants