A novel function of emodin: enhancement of the nucleotide excision repair of UV- and cisplatin-induced DNA damage in human cells.
Nucleotide excision repair (NER) is the main pathway by which mammalian cells 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 repair of UV- and cisplatin-induced DNA damage in human fibroblast cells (WI38) was evaluated. Emodin increased unscheduled DNA synthesis (UDS) of UV-treated cells and reduced cisplatin-induced DNA adducts in WI38 in a concentration-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 emodin treatment were determined by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers. Among the subunits, the expression of ERCC1 in WI38 cells was up-regulated significantly after emodin treatment. All other expressions remained essentially unchanged. In addition, calcium influx in WI38 was increased in proportion to the concentration of emodin. 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 human cells, and elevated ERCC1 gene expression and Ca2+-mediated DNA repair processes may be involved in the repair mechanism of emodin.
Chang
L C
LC
Department of Biochemistry, Kaohsiung Medical College, Taiwan.
Sheu
H M
HM
Huang
Y S
YS
Tsai
T R
TR
Kuo
K W
KW
D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D004249:DNA Damage / Q000528:radiation effects; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D004642:Emodin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008969:Molecular Sequence Data; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D004247:DNA; D011088:DNA Ligases; D004642:Emodin; D002945:Cisplatin; D002118:Calcium