@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.}
}
@article {2703,
	title = {CHEMICAL AND BIOLOGICAL EVIDENCE LINKS MICROCYSTINS TO SALMON NETPEN LIVER-DISEASE},
	journal = {Toxicon},
	volume = {31},
	number = {10},
	year = {1993},
	note = {ISI Document Delivery No.: MH840Times Cited: 89Cited Reference Count: 16},
	month = {Oct},
	pages = {1315-1323},
	type = {Article},
	abstract = {Evidence is presented that links microcystins to a severe liver disease that occurs in Atlantic salmon that are netpen-reared in coastal British Columbia. Liquid chromatography-linked protein phosphatase bioassay analysis of extracts of liver tissue taken from Atlantic salmon afflicted with netpen liver disease showed the presence of an inhibitor of protein phosphatase that was chromatographically indistinguishable from microcystin-LR. Analysis of liver tissue from healthy control fish showed a complete absence of microcystin-LR. Intraperitoneal injection of microcystin-LR into healthy Atlantic salmon re-created the pathologic changes of netpen liver disease, including diffuse necrosis and hepatic megalocytosis.},
	keywords = {PHOSPHATASE, RAINBOW-TROUT},
	isbn = {0041-0101},
	url = {<Go to ISI>://A1993MH84000011},
	author = {Andersen, R. J. and Luu, H. A. and Chen, D. Z. X. and Holmes, C. F. B. and Kent, M. L. and Leblanc, M. and Taylor, Fjrm and Williams, D. E.}
}
