Cudraflavanone A purified from Cudrania tricuspidata induces apoptotic cell death of human leukemia U937 cells, at least in part, through the inhibition of DNA topoisomerase I and protein kinase C activity.
A chloroform extract of the root bark of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2S-2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-6-prenyl flavanone (cudraflavanone A). Cudraflavanone A was shown to inhibit the activity of topoisomerase I with approximately 0.4 mmol/l 50% inhibitory concentration. A concentration of 6 micromol/l cudraflavanone A caused a 50% growth inhibition of human cancer cell U937. Cudraflavanone A-induced cell death was characterized by the cleavage of poly(ADP-ribose) polymerase and pro-caspase-3. Furthermore, cudraflavanone A induced the fragmentation of DNA into multiples of 180 bp (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by cudraflavanone A was also confirmed using flow-cytometry analysis. In addition, this compound inhibited protein kinase C activity with approximately 150 micromol/l 50% inhibitory concentration. Taken together, these results suggest that cudraflavanone A may function by inhibiting oncogenic disease, at least in part, through the inhibition of protein kinase C and topoisomerase I activity.
Rho
Youn-Hwa
YH
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Daegu.
Lee
Byong-Won
BW
Park
Ki-Hun
KH
Bae
Young-Seuk
YS
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D029586:Moraceae / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D059004:Topoisomerase I Inhibitors; D020298:U937 Cells
D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D010936:Plant Extracts; D059004:Topoisomerase I Inhibitors; C524510:cudraflavanone A; D011493:Protein Kinase C