The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.
The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.
Gliszczyńska-Swigło
Anna
A
Division of Toxicology, Wageningen University, 5, 6703 HE Wageningen, Tuinlaan, The Netherlands. a.gliszczynska-swiglo@ae.poznan.pl
van der Woude
Hester
H
de Haan
Laura
L
Tyrakowska
Bozena
B
Aarts
Jac M M J G
JM
Rietjens
Ivonne M C M
IM
D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D006224:Cricetinae; D003470:Culture Media; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D011419:Propidium; D011794:Quercetin / Q000737:chemistry* / Q000633:toxicity*; D011809:Quinones / Q000737:chemistry*; D024483:Vitamin K 3 / Q000633:toxicity
D004396:Coloring Agents; D003470:Culture Media; D011809:Quinones; D011419:Propidium; D024483:Vitamin K 3; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone)