Antiproliferative activity of L-asparaginase of Tetrahymena pyriformis on human breast cancer cell lines.
Purified L-asparaginase of Tetrahymena pyriformis is a multi-subunit enzyme exhibiting protein kinase activity as well. The enzyme's L-asparaginase activity is affected by its phosphorylation state. Both native and dephosphorylated L-asparaginase show antiproliferative activity on three breast cancer cell lines (T47D, BT20 and MCF-7) and on Walker 256 cells. These cells do not possess measurable L-asparaginase or L-asparagine synthetase activity. When T47D cells are treated for different times with L-asparaginase and then placed in fresh medium, the growth of cells treated for 1, 3, or 6 hours is initiated and parallels control curve, while the growth of cells treated for 24 or 48 hours with L-asparaginase stays at the same inhibitory level (24 h treatment) or continues to drop (48 h treatment). Addition of D-asparagine, a competitive inhibitor of T. pyriformis L-asparaginase, counteracts the antiproliferative activity of L-asparaginase, indicating that L-asparaginase and not the kinase activity is responsible for that effect.
Kyriakidis
D A
DA
Laboratory of Biochemistry, Faculty of Chemistry, Aristotelian University of Thessaloniki, Greece.
Tsirka
S A
SA
Tsavdaridis
I K
IK
Iliadis
S N
SN
Kortsaris
A H
AH
D000818:Animals; D001215:Asparaginase / Q000378:metabolism*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D013769:Tetrahymena pyriformis / Q000201:enzymology; D014407:Tumor Cells, Cultured
D011494:Protein Kinases; D001215:Asparaginase