Apoptotic cell death of human leukaemia U937 cells by ubiquinone-9 purified from Pleurotus eryngii

• Published in: Natural product research Vol. 23; no. 12; pp. 1112 - 1119
• Main Authors: Bae, Jeen-Soo, Park, Jin Wook, Park, So Hyun, Park, Jung Bin, Rho, Yoon-Hwa, Ryu, Young Bae, Lee, Kun-Sik, Park, Ki-Hun, Bae, Young-Seuk
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.01.2009
• Subjects: anticancer drug; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Blotting, Western; DNA Fragmentation; DNA topoisomerase I inhibitor; DNA Topoisomerases, Type I - metabolism; Enzyme Activation - drug effects; Flow Cytometry; human leukaemia cells; Humans; Molecular Structure; Pleurotus - chemistry; Pleurotus eryngii; U937 Cells; Ubiquinone - chemistry; Ubiquinone - isolation & purification; Ubiquinone - pharmacology; ubiquinone-9
• ISSN: 1478-6419; 1478-6427
• DOI: 10.1080/14786410802417107

A chloroform extract of the edible mushroom Pleurotus eryngii showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as ubiquinone-9. Ubiquinone-9 was shown to inhibit the activity of topoisomerase I with IC 50 of about 50 µM. Concentration of 110 µM ubiquinone-9 caused 50% growth inhibition of human leukaemia U937 cells, but not that of normal fibroblast NIH3T3 and 3Y1 cells. Ubiquinone-9-induced cell death was characterised with the cleavage of poly (ADP-ribose) polymerase and pro-caspase 3. Furthermore, ubiquinone-9 induced the fragmentation of DNA into an apoptotic DNA ladder, indicating that the inhibitor triggered apoptosis. The induction of apoptosis by ubiquinone-9 was also confirmed using flow cytometry analysis. Taken together, these results suggest that ubiquinone-9 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.