Autor: |
Palma TV; Postgraduate Program in Biological Sciences: Biochemistry Toxicology, Biochemistry and Oxidative Stress Section of the Therapy Laboratory Cellular, Federal University of Santa Maria, Santa Maria, RS, Brazil., Lenz LS; Postgraduate Program in Biological Sciences: Biochemistry Toxicology, Biochemistry and Oxidative Stress Section of the Therapy Laboratory Cellular, Federal University of Santa Maria, Santa Maria, RS, Brazil., Bottari NB; Postgraduate Program in Biological Sciences: Biochemistry Toxicological, Department of Chemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil., Pereira A; Postgraduate Program in Biological Sciences: Biochemistry Toxicological, Department of Chemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil., Schetinger MRC; Postgraduate Program in Biological Sciences: Biochemistry Toxicological, Department of Chemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil., Morsch VM; Postgraduate Program in Biological Sciences: Biochemistry Toxicological, Department of Chemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil., Ulrich H; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil., Pillat MM; Department of Microbiology and Parasitology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil. mmpillat@gmail.com., de Andrade CM; Department of Small Animal Clinic, Center of Rural Sciences, Federal University of Santa Maria-RS, Room 121, Veterinary Hospital Building, Avenue Roraima No. 1000, Santa Maria, RS, 97105900, Brazil. cmelazzoandrade1@gmail.com. |
Abstrakt: |
Glioblastoma multiforme (GM) is the most prevalent tumor among gliomas and presents the highest mortality rate among brain tumors. Berberine (BBR) is an alkaloid isoquinoline found in medicinal plants such as Coptis chinensis. Studies have been showed that BBR presents protective activity in mesenchymal cells and neurons, and antitumor properties in breast cancer and hepatocarcinoma. The aim of this study was to investigate the antitumor effects of BBR in GM U87MG cells, as well as to identify, whether such effects are mediated by oxidative stress and canonical apoptotic pathways. After treatment with several concentrations of BBR (10, 25, 100 and 250 µM) for 24, 48 and 72 h of exposure, BBR reduce cell viability of U87MG cells in a concentration- and time-dependent manner. Afterwards, it was observed that BBR, starting at a concentration of 25 µM of 24 h exposure, significantly suppressed proliferation and increased early apoptosis (53.5% ± 11.15 of annexin V + propidium iodide - cells) compared to untreated cells (7.5% ± 4.6). BBR-induced apoptosis was independent from AMPK activity and did not change total caspase-3 and p-p53 levels. Moreover, BBR (25 μM/24 h) increased oxidative stress in U87MG cells, evidenced by high levels of reactive oxygen species, thiobarbituric acid reactive substance and protein carbonylation. Considering the antitumor effects of BBR in U87MG cells, this compound may be a potential candidate for adjuvant GM treatment. |