A novel function of emodin - Enhancement of the nucleotide excision repairof UV- and cisplatin-induced DNA damage in human cells

Nucleotide excision repair (NER) is the main pathway by which mammalian cel ls remove carcinogenic DNA lesions caused by UV light and many other common mutagens. To explore the effect of emodin on NER, its influence on the rep air of UV- and cisplatin-induced DNA damage in human fibroblast cells (W138 ) was evaluated. Emodin increased unscheduled DNA synthesis (UDS) of UV-tre ated cells and reduced cisplatin-induced DNA adducts in WI38 in a concentra tion-dependent manner, indicating that emodin might promote NER capability in cells. The resultant NER complex is a cooperative assembly of XPF, ERCC1 , XPA, RPA, and XPG subunits. The gene regulations of the subunits after em odin treatment were determined by reverse transcription-polymerase chain re action (RT-PCR) using specific primers. Among the subunits, the expression of ERCC1 in WI38 cells was up-regulated significantly after emodin treatmen t. All other expressions remained essentially unchanged. In addition, calci um influx in WI38 was increased in proportion to the concentration of emodi n. Since UV-induced NER is Ca2+ dependent, elevation of calcium influx may be another mechanism by which emodin facilitates DNA repair. In conclusion, emodin can increase the repair of UV and cisplatin-induced DNA damage in h uman cells, and elevated ERCC1 gene expression and Ca2+-mediated DNA repair processes may be involved in the repair mechanism of emodin. BIOCHEM PHARM ACOL 58;1:49-57, 1999. (C) 1999 Elsevier Science Inc.