A non-characteristic response of L1210 cells to lovastatin.
Isoprenylated proteins are believed to play an important role in DNA synthesis and subsequent cell cycle progression. Inhibition of the biosynthesis of these isoprenylated proteins results in a decrease in DNA synthesis and a characteristic G1 blockade of the cell cycle. This inhibition can be achieved by incubation of cells in the presence of a hydroxy-methylglutaryl-coenzyme A reductase inhibitor (lovastatin) and can be reversed by addition of exogenous mevalonate. When incubated in the presence of lovastatin, L1210 wild-type cells are not inhibited at G1 but rather progress to a G2/M blockade, which is reversible with exogenous mevalonate. Thymidine incorporation has also shown that DNA synthesis is occurring until this blockade is achieved. However, when L1210 cells resistant to cisplatin are incubated in the presence of lovastatin, the characteristic G1 cell cycle blockade and DNA synthesis inhibition occur. The understanding of this mechanism and the role that isoprenylated proteins play in the regulation of DNA synthesis and cell cycle progression may gain great insight into the abnormal control of the cancer cell.
Engelke
K J
KJ
Department of Pharmacology, University of Vermont, Burlington 05405.
Hacker
M P
MP
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D016193:G1 Phase; D016195:G2 Phase; D007700:Kinetics; D007939:Leukemia L1210 / Q000473:pathology*; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis; D017368:Protein Prenylation; D016196:S Phase; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D008148:Lovastatin; D008798:Mevalonic Acid; D013936:Thymidine