@article {5181,
	title = {G(2) DNA damage checkpoint inhibition and antimitotic activity of 13-hydroxy-15-oxozoapatlin},
	journal = {Journal of Biological Chemistry},
	volume = {276},
	number = {51},
	year = {2001},
	note = {ISI Document Delivery No.: 505QLTimes Cited: 24Cited Reference Count: 51},
	month = {Dec},
	pages = {48231-48236},
	type = {Article},
	abstract = {Checkpoints activated in response to DNA damage cause arrest in the G(1) and G(2) phases of the cell cycle. Inhibitors of the G(2) checkpoint may be used as tools to study this response and also to increase the effectiveness of DNA-damaging therapies against cancers lacking p53 function. Using a cell-based assay for G(2) check. point inhibitors, we have screened extracts from the NCI National Institutes of Health Natural Products Repository and have identified 13-hydroxy-15-oxozoapatlin (OZ) from the African tree Parinari curatellifolia. Flow cytometry with a mitosis-specific antibody showed that checkpoint inhibition by OZ was maximal at 10 muM, which released 20\% of irradiated MCF-7 cells expressing defective p53 and 30\% of irradiated HCT116p53(-/-) cells from G(2) arrest. OZ additively increased the response to the checkpoint inhibitors isogranulatimide and debromohymenialdisine, but it did not augment the effects of UCN-01 or caffeine. Unlike other checkpoint inhibitors, OZ did not inhibit ataxia-telangiectasia mutated (ATM), ATM and Rad3-related (ATR), Chk1, Chk2, Plk1, or Ser/Thr protein phosphatases in vitro. Treatment with OZ also caused G(2)-arrested and cycling cells to arrest in mitosis in a state resembling prometaphase. In these cells, the chromosomes were condensed and scattered over disordered mitotic spindles. The results demonstrate that OZ is both a G(2) checkpoint inhibitor and an antimitotic agent.},
	keywords = {ARREST, BHK CELLS, CAFFEINE, CELL-CYCLE CHECKPOINTS, CHROMOSOME ALIGNMENT, G2, P34(CDC2) KINASE, PROTEIN-KINASE, RADIOSENSITIZING AGENT, TYROSINE KINASE, UCN-01},
	isbn = {0021-9258},
	url = {<Go to ISI>://000172927000066},
	author = {Rundle, N. T. and Xu, L. and Andersen, R. J. and Roberge, M.}
}
@article {5042,
	title = {Inhibition of the G(2) DNA damage checkpoint and of protein kinases Chk1 and Chk2 by the marine sponge alkaloid debromohymenialdisine},
	journal = {Journal of Biological Chemistry},
	volume = {276},
	number = {21},
	year = {2001},
	note = {ISI Document Delivery No.: 435FJTimes Cited: 78Cited Reference Count: 61},
	month = {May},
	pages = {17914-17919},
	type = {Article},
	abstract = {Cells can respond to DNA damage by activating checkpoints that delay cell cycle progression and allow time for DNA repair. Chemical inhibitors of the G(2) phase DNA damage checkpoint may be used as tools to understand better how the checkpoint is regulated and may be used to sensitize cancer cells to DNA-damaging therapies. However, few inhibitors are known. We used a cell-based assay to screen natural extracts for G(2) checkpoint inhibitors and identified debromohymenialdisine (DBH) from a marine sponge. DBH is distinct structurally from previously known G(2) checkpoint inhibitors. It inhibited the G(2) checkpoint with an IC50 of 8 muM and showed moderate cytotoxicity (IC50 = 25 muM) toward MCF-7 cells. DBH inhibited the checkpoint kinases Chk1 (IC50 = 3 muM) and Chk2 (IC50 = 3.5 muM) but not ataxia-telangiectasia mutated (ATM), ATM-Rads-related protein, or DNA-dependent protein kinase in vitro, indicating that it blocks two major branches of the checkpoint pathway downstream of ATM. It did not cause the activation or inhibition of different signal transduction proteins, as determined by mobility shift analysis in Western blots, suggesting that it inhibits a narrow range of protein kinases in vivo.},
	keywords = {14-3-3 BINDING, BHK CELLS, CDC25, CELL-CYCLE CHECKPOINTS, CHROMOSOME, CONDENSATION, DEPENDENT KINASES, H3 PHOSPHORYLATION, INDUCED MITOTIC DELAY, MAMMALIAN-CELLS, PHOSPHATASE, RADIOSENSITIZING AGENT},
	isbn = {0021-9258},
	url = {<Go to ISI>://000168866500042},
	author = {Curman, D. and Cinel, B. and Williams, D. E. and Rundle, N. and Block, W. D. and Goodarzi, A. A. and Hutchins, J. R. and Clarke, P. R. and Zhou, B. B. and Lees-Miller, S. P. and Andersen, R. J. and Roberge, M.}
}
