Inhibition of thymidine kinase in cultured mammary tumor cells by the chemopreventive organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate.
To identify mechanisms by which the organoselenium compound 1,4-phenylenebis(methylene)selenocyanate (p-XSC) mediates its chemopreventive activities, we have examined its effects on cell lines derived from breast cancer of humans and rats. When log-phase cells were treated with a dose of 1 microM p-XSC, we observed a significant decrease in thymidine kinase (TK) activity within 4 h, and reduced thymidine incorporation after 24-48 h. When the dose of p-XSC was increased to 2 microM, the decrease in TK was accompanied by a modest, but significant, decrease in thymidine incorporation at 4 h, and a greater inhibition after 24-48 h. At a dose of > or = 3 microM, we observed a large decrease in TK, accompanied by > 70% reduction in thymidine incorporation, as well as decreases in mitochondrial activity and cell numbers, all within 4 h. Equal concentrations of selenium in the form of Na2SeO3 had no effect on the parameters described above. These data suggest that inhibition of thymidine kinase is an early effect of p-XSC in cultured breast tumor cells.
Tillotson
J K
JK
American Health Foundation, Valhalla, NY 10595.
Upadhyaya
P
P
Ronai
Z
Z
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D006131:Growth Inhibitors; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*
D006131:Growth Inhibitors; D016566:Organoselenium Compounds; C074153:1,4-phenylenebis(methylene)selenocyanate; D000255:Adenosine Triphosphate; D013937:Thymidine Kinase; D013936:Thymidine