Pyrrolidine dithiocarbamate induces cyclooxygenase-2 expression in NIH 3T3 fibroblast cells.
Pyrrolidine dithiocarbamate (PDTC) is a metal chelating compound that can exert either pro-oxidant or antioxidant effects in different situations. Several studies demonstrate that it can inhibit cyclooxygenase-2 (COX-2) expression, which may be due to its antioxidant activity. Here, we found that PDTC rather increased COX-2 expression in NIH 3T3. The increase of COX-2 expression was inhibited by adding bathocuproline disulfonic acid, a non-permeable specific copper chelator, in the incubation medium. This result suggests that PDTC exerts its effect by transporting redox-active copper ions into the cells. In support of this observation, PDTC did not induce COX-2 expression in a serum-free environment. When PDTC was added with copper in the serum-free medium, it acted as the inducer of COX-2 expression. In addition, pretreatment of N-acetyl-L-cystein or dithiothreitol, other antioxidants, inhibited the PDTC-induced COX-2 expression. Our data indicate that PDTC induces COX-2 expression in NIH 3T3 cells, which may be due to its activities as a copper chelator and a pro-oxidant.
Lee
Jeong Eun
JE
Department of Microbiology, Keimyung University School of Medicine, 194 Dongsan-Dong, Taegu 700-712, Republic of Korea.
Kim
Kyung Min
KM
Cho
Jae-We
JW
Suh
Seong-Il
SI
Suh
Min-Ho
MH
Kwon
Taeg Kyu
TK
Park
Jong-Wook
JW
Bae
Jae Hoon
JH
Song
Dae Kyu
DK
Cho
Chi-Heum
CH
Bae
Insoo
I
Baek
Won-Ki
WK
D016475:3T3 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000502:physiology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000201:enzymology; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008670:Metals / Q000494:pharmacology; D051379:Mice; D016877:Oxidants / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013859:Thiocarbamates / Q000494:pharmacology*
D000975:Antioxidants; D002614:Chelating Agents; D007527:Isoenzymes; D008670:Metals; D016877:Oxidants; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D003300:Copper; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D004229:Dithiothreitol; D000111:Acetylcysteine