Apoptotic cell death of human leukaemia U937 cells by ubiquinone-9 purified from Pleurotus eryngii.
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 microM. Concentration of 110 microM 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.
Bae
Jeen-Soo
JS
Daegu Science High School, Daegu, Korea.
Park
Jin Wook
JW
Park
So Hyun
SH
Park
Jung Bin
JB
Rho
Yoon-Hwa
YH
Ryu
Young Bae
YB
Lee
Kun-Sik
KS
Park
Ki-Hun
KH
Bae
Young-Seuk
YS
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053938:DNA Fragmentation; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D015394:Molecular Structure; D020076:Pleurotus / Q000737:chemistry*; D020298:U937 Cells; D014451:Ubiquinone / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014451:Ubiquinone; D004264:DNA Topoisomerases, Type I; C030571:ubiquinone 9