Abstract |
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.
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Authors | Youn-Hwa Rho, Byong-Won Lee, Ki-Hun Park, Young-Seuk Bae |
Journal | Anti-cancer drugs
(Anticancer Drugs)
Vol. 18
Issue 9
Pg. 1023-8
(Oct 2007)
ISSN: 0959-4973 [Print] England |
PMID | 17704652
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Flavanones
- Plant Extracts
- Topoisomerase I Inhibitors
- cudraflavanone A
- Protein Kinase C
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Topics |
- Antineoplastic Agents, Phytogenic
(isolation & purification, pharmacology)
- Apoptosis
(drug effects)
- Cell Survival
(drug effects)
- DNA Fragmentation
(drug effects)
- Flavanones
(isolation & purification, pharmacology)
- Humans
- Molecular Structure
- Moraceae
(chemistry)
- Plant Bark
(chemistry)
- Plant Extracts
(isolation & purification, pharmacology)
- Plant Roots
(chemistry)
- Protein Kinase C
(antagonists & inhibitors)
- Topoisomerase I Inhibitors
- U937 Cells
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