Mitochondrially targeted effects of berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium] on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions.

作者: Gonçalo C. Pereira , Ana F. Branco , Júlio A. C. Matos , Sandro L. Pereira , Donna Parke

DOI: 10.1124/JPET.107.128017

关键词:

摘要: Berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a)quinolizinium] is an alkaloid present in plant extracts and has a history of use traditional Chinese Native American medicine. Because its ability to arrest the cell cycle cause apoptosis several malignant lines, it received attention as potential anticancer therapeutic agent. Previous studies suggest that mitochondria may be important target berberine, but relatively little known about extent or molecular mechanisms berberine-mitochondrial interactions. The objective work was investigate interaction berberine with mitochondria, both situ isolated mitochondrial fractions. data show selectively accumulated by which accompanied proliferation, fragmentation depolarization, oxidative stress, decrease ATP levels. Electron microscopy berberine-treated cells shows reduction mitochondria-like structures, DNA copy number. Isolated fractions treated had slower respiration, especially when complex I substrates were used, increased I-dependent stress. It also demonstrated for first time stimulates permeability transition. Direct effects on ATPase activity not detected. demonstrates number previously unknown alterations physiology induced chemotherapeutic agent, although suggests high doses should used without proper toxicology assessment.

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