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Rho YH, Yoon SH, Kim EK, Kang JY, Lee BW, Park KH, Bae YS: 2',5,7-Trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone purified from Cudrania tricuspidata induces apoptotic cell death of human leukemia U937 cells. Nat Prod Res. 2007 Jun;21(7):616-24.
Cellular DNA topoisomerase I is an important target in cancer chemotherapy. A chloroform extract of the root barks of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone. The compound, temporarily designated as PKH-3, was shown to inhibit the activity of topoisomerase I with IC50 about 1.0 mM. Concentration of 10 microM PKH-3 caused 50% growth inhibition of human cancer cell U937. PKH-3-induced cell death was characterized with the cleavage of poly (ADP-ribose) polymerase (PARP) and pro-caspase 3. Furthermore, PKH-3 induced the fragmentation of DNA into multiples of 180 b.p. (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by PKH-3 was also confirmed using flow cytometry analysis. Taken together, these results suggest that PKH-3 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity. |
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