Berberine induces apoptosis in glioblastoma multiforme U87MG cells via oxidative stress and independent of AMPK activity

Autor(es)

Palma, Tais Vidal ^[1] ; Lenz, Luana Sueling ^[1] ; Bottari, Nathiele Bianchin ^[2] ; Pereira, Aline ^[2] ; Schetinger, Maria Rosa Chitolina ^[2] ; Morsch, Vera Maria ^[2] ; Ulrich, Henning ^[3] ; Pillat, Micheli Mainardi ^[4] ; de Andrade, Cinthia Melazzo ^[5]

Afiliação do(s) autor(es)

^[1] Univ Fed Santa Maria, Biochem & Oxidat Stress Sect Therapy Lab Cellular, Postgrad Program Biol Sci Biochem Toxicol, Santa Maria, RS - Brazil

^[2] Univ Fed Santa Maria, Dept Chem, Postgrad Program Biol Sci Biochem Toxicol, Ctr Nat & Exact Sci, Santa Maria, RS - Brazil

^[3] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, SP - Brazil

^[4] Univ Fed Santa Maria, Dept Microbiol & Parasitol, Hlth Sci Ctr, Santa Maria, RS - Brazil

^[5] Fed Univ Santa Maria RS, Dept Small Anim Clin, Ctr Rural Sci, Room 121, Vet Hosp Bldg, Ave Roraima 1000, Santa Maria 97105900, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR BIOLOGY REPORTS; v. 47, n. 6 MAY 2020.
• Citações Web of Science: 0

Resumo

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 mu M) 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 mu M 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 mu M/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. (AU)

• Processo FAPESP: 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático