Camptothecin causes cell cycle perturbations within T-lymphoblastoid cells followed by dose dependent induction of apoptosis.
We have investigated the effect of the anticancer compound, camptothecin on Jurkat T-cells, a lymphoblastoid leukemic cell-line. Exposure to low concentrations led to rapid cessation of DNA (more than 95%) and RNA (more than 75%) synthesis. Perturbations to the cell cycle were observed following exposure which caused a significant accumulation of cells within G1 (P = 0.03) with a concomitant decrease in G2/M (P = 0.025). Concentrations below 0.1 microM could inhibit DNA synthesis but not induce apoptosis. Induction of apoptosis was dose dependent and could be detected as early as 3 h post exposure. The apoptotic population appeared to be derived from G1 and S-phase cells but not G2/M, coinciding with the cell cycle compartments in which DNA and RNA polymerases function. However, direct inhibition of DNA polymerase alone was not shown to be associated the induction of apoptosis or with a decrease in susceptibility to camptothecin-induced cell death. The effects of camptothecin on Jurkat T-cells and the potential mechanisms involved are discussed in the context of observations made in other transformed cell lines.
Johnson
N
N
Department of Immunology, Royal London College of Medicine and Dentistry, U.K.
Ng
T T
TT
Parkin
J M
JM
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D016590:Aphidicolin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival; D053938:DNA Fragmentation; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D012313:RNA / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D016590:Aphidicolin; D012313:RNA; D002166:Camptothecin