Chrysin as an Anti-Cancer Agent Exerts Selective Toxicity by Directly Inhibiting Mitochondrial Complex II and V in CLL B-lymphocytes

• Published in: Cancer investigation Vol. 35; no. 3; pp. 174 - 186
• Main Authors: Salimi, Ahmad, Roudkenar, Mehryar Habibi, Seydi, Enayatollah, Sadeghi, Leila, Mohseni, Alireza, Pirahmadi, Nahal, Pourahmad, Jalal
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 16.03.2017
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphatases - antagonists & inhibitors; Adenosine Triphosphate - metabolism; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; B-Lymphocytes - drug effects; B-Lymphocytes - physiology; Carrier Proteins - antagonists & inhibitors; Caspase 3 - metabolism; Cell Survival - drug effects; Chrysin; CLL; complex II; complex V; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Electron Transport Complex II - antagonists & inhibitors; Flavonoids - pharmacology; Humans; Inhibitory Concentration 50; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Membrane Potential, Mitochondrial - drug effects; Membrane Proteins - antagonists & inhibitors; mitochondria; Mitochondrial Swelling - drug effects; Oxidative Phosphorylation; Reactive Oxygen Species - metabolism; Tumor Cells, Cultured; CLL; Chrysin; complex V; mitochondria; complex II
• ISSN: 0735-7907; 1532-4192
• DOI: 10.1080/07357907.2016.1276187

We investigated the effect of chrysin on isolated normal and chronic lymphocytic leukemia (CLL) B-lymphocytes and their isolated mitochondria. We report that a selective and significant increase in cytotoxicity, intracellular reactive oxygen species, mitochondrial membrane potential collapse, ADP/ATP ratio, caspase 3 activation and finally apoptosis in chrysin-treated CLL B- lymphocytes. Also we determined that chrysin selectively inhibits complex II and ATPases in cancerous mitochondria. In this study we proved that the ability of chrysin to promote apoptosis in CLL B-lymphocytes performed by selectively targeting of mitochondria. Our findings may provide a potential therapeutic approach for using chrysin to target mitochondria in CLL B-lymphocytes.