Early 5-fluorouracil-induced changes of poly(A) polymerase in HeLa and WISH cells.
5-Fluorouracil (5-FU), a drug with numerous mechanisms of action which has a long-term suppressive effect on human cancer cell proliferation, mediates both partial dephosphorylation and inactivation of poly(A) polymerase (PAP) [EC. 2.7.7.19] as detected by immunoblotting analysis and non-specific enzyme assay, respectively, in human carcinoma HeLa and diploid WISH cells at a concentration of 100 microM. When the same experiment is done in the presence of phosphatase inhibitors, 5-FU-induced partial PAP dephosphorylation is abolished. Moreover, a cell type-modulated, differential response of HeLa cells (5-FU chemosensitive cells) versus WISH cells (drug-resistant diploid cells) is observed. These results suggest that 5-FU induces early direct or indirect changes in the structure and function of PAP and may regulate pre-mRNA cleavage-polyadenylation.
Balatsos
N A
NA
Institute of Biology, NCSR Demokritos, Aghia Paraskevi Attikis, Greece.
Havredaki
M
M
Tsiapalis
C M
CM
D000469:Alkaline Phosphatase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D005562:Formazans; D006367:HeLa Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism*; D013778:Tetrazolium Salts; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
D005562:Formazans; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D013778:Tetrazolium Salts; C079782:MTT formazan; D011062:Polynucleotide Adenylyltransferase; D000469:Alkaline Phosphatase; D005472:Fluorouracil