Redox regulation of cell proliferation by pyrrolidine dithiocarbamate in murine thymoma cells transplanted in vivo.
Pyrrolidine dithiocarbamate (PDTC) is a synthetic compound largely used in cell biological studies and known to exert either antioxidant or pro-oxidant effects. Recently, its antitumoral activity has been proposed on the basis of its antioxidant and proapoptotic effects. In the present study, we evaluated the effect of increasing i.p. doses of PDTC on the growth of a strain of highly malignant thymoma cells inoculated in the peritoneum of inbred Balb/c mice. PDTC treatment increased the number of thymoma cells in a dose-dependent manner, enhancing the percentage of proliferating tumor cells. PDTC exerted regulatory effects on cell cycle distribution, decreasing the expression of cell cycle inhibitors. Alterations in the production of intracellular reactive oxygen species, levels of oxidized glutathione, and intracellular levels of the redox-active metals iron and copper were also observed. The above results represent the first evidence that PDTC may induce in vivo cell proliferation in a murine thymoma cell model. In addition, we suggest that the ability of PDTC to bind and transport metals inside the cell and its pro-oxidant property may be factors underlying its effects on thymoma cell proliferation and cell cycle distribution.
Di Nicuolo
F
F
Institute of General Pathology, Catholic University, Rome, Italy.
Serini
S
S
Boninsegna
A
A
Palozza
P
P
Calviello
G
G
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis; D002455:Cell Division / Q000187:drug effects*; D003300:Copper / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000032:analysis; D004791:Enzyme Inhibitors / Q000032:analysis; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010084:Oxidation-Reduction; D011759:Pyrrolidines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology*; D013945:Thymoma / Q000473:pathology*; D013953:Thymus Neoplasms / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000032:analysis
C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C020972:pyrrolidine dithiocarbamic acid; D003300:Copper; D007501:Iron; D018844:Cyclin-Dependent Kinases; D005978:Glutathione