Efeito antitumoral e modulação do status redox do extrato de Rubus sp. (amora-preta) em linhagens celulares de glioblastoma

Abstract

Glioblastoma (GBM) is a highly malignant brain tumor due to its aggressive behavior, manifested by intense cell division activity, the ability to form new blood vessels, and a tendency to invade surrounding tissues, with a common observation of frequently limited response to conventional oncological treatment. Furthermore, the combination of tumor aggressiveness with limited treatment options results in a low survival rate for patients, between 12 to 15 months. In this perspective, Rubus sp. (blackberry) has become the subject of studies as a therapeutic alternative for GBM treatment, considering its rich composition of bioactive compounds with well-described antioxidant and antineoplastic properties in other neoplasms. Thus, the present study aimed to investigate the potential antitumoral effects of blackberry methanolic extract regarding rat (C6) and human (U87) glioma cell lines. Cells from C6 and U87 glioma cell lines were exposed to blackberry methanolic extract at concentrations ranging from 125 to 2000 µg/mL for 24 h, 48 h, and/or 72 h. Cell viability and biomass were evaluated in cancer cell lines and primary culture of astrocytes. Additionally, parameters of oxidative stress, colony formation, cell proliferation, and migration, as well as interleukin 10 levels in the C6 cell line were assessed. Initially, no changes in viability or cell biomass were observed in cultures of healthy astrocytes exposed to blackberry extract, indicating its non-toxic nature. On the other hand, blackberry extract, for the C6 cell line, reduced cell viability and biomass from concentrations of 750 µg/mL and 500 µg/mL respectively, and for the U87 cell line, at concentrations of 125-2000 µg/mL. After 72 hours of treatment, a reduction in reactive species was observed in the C6 cell line at all tested concentrations, an increase in sulfhydryl content at concentrations of 1500 and 2000 µg/mL, as well as an elevation in the activity of the enzyme’s glutathione S-transferase, superoxide dismutase, and catalase in the three highest concentrations. Regarding colony formation, a reduction in size and number was observed in C6 cells. Regarding cell migration, an attenuation was observed after 6 hours of treatment with 125 µg/mL of blackberry extract. Furthermore, a significant reduction in interleukin 10 levels was observed at all tested concentrations. Thus, blackberry extract emerges as a promising compound in the therapeutic approach to GBM.