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

• Published in: International journal of molecular sciences 2020-07, Vol.21 (13), p.4713
• Main Authors: Izumi, Clarice, Laure, Helen Julie, Barbosa, Nayara Gonçalves, Thomé, Carolina Hassibe, Ferreira, Germano Aguiar, Sousa, João Paulo Barreto, Lopes, Norberto Peporine, Rosa, José César
• Format: Article
• Language: English
• Subjects: Antibodies; Antineoplastic Agents - pharmacology; Antiproliferatives; Apoptosis; Asteraceae; Blood-brain barrier; Blood-Brain Barrier - metabolism; Brain cancer; Brain Neoplasms - metabolism; Brain tumors; Brazil; Bridged-Ring Compounds - pharmacology; Catabolism; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Chemotherapy; Drug development; Drug dosages; Efficiency; Furans - pharmacology; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - metabolism; glioblastoma cells; Glioma; Glioma - metabolism; Glycolysis; Humans; Lactones; Lactones - metabolism; Lactones - pharmacology; Low molecular weights; Molecular weight; Natural products; Plant Extracts - pharmacology; Proteins; proteomics; Radiation therapy; sesquiterpene lactone; Sesquiterpene lactones; Sesquiterpenes - pharmacology; Sesterterpenes - pharmacology; Temozolomide; unfolded protein response; Vernonia - metabolism; Vernonia - physiology; Wound healing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21134713

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 from spp., 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.