Berberine induces apoptosis in glioblastoma multiforme U87MG cells via oxidative stress and independent of AMPK activity
- 14 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Biology Reports
- Vol. 47 (6), 4393-4400
- https://doi.org/10.1007/s11033-020-05500-9
Abstract
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.Keywords
Funding Information
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2018/07366-4)
This publication has 29 references indexed in Scilit:
- Metabolic phenotypes in primary unknown metastatic carcinomaJournal of Translational Medicine, 2014
- In vitro biological assessment of berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effectsBMC Complementary and Alternative Medicine, 2013
- Interaction of Herbal Compounds with Biological Targets: A Case Study with BerberineThe Scientific World Journal, 2012
- Redox Regulation of the AMP-Activated Protein KinasePLOS ONE, 2010
- The alkaloid Berberine inhibits the growth of Anoikis-resistant MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell cycle arrestPhytomedicine, 2010
- Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissueNature Protocols, 2009
- Improved analysis of malondialdehyde in human body fluidsFree Radical Biology & Medicine, 1996
- An assay for superoxide dismutase activity in mammalian tissue homogenatesAnalytical Biochemistry, 1989
- Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assaysJournal of Immunological Methods, 1983
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976