Calcium ionophores at concentrations mitogenic to normal murine T cells inhibit the proliferation of tumor cells in vitro.
The Ca2+ ionophores, A23187 and ionomycin, when used alone at 0.3-5 microM concentrations, were mitogenic to normal resting murine T cells. At these doses, the Ca2+ ionophores inhibited DNA synthesis and growth of a T cell lymphoma and several murine transformed cell lines. Treatment of tumor cells with either ionophore caused a rapid increase in intracellular Ca2+ [( Ca2+]i) followed by a decline and, thereafter, maintenance of a steady level that was slightly above the preactivation levels of [Ca2+]i. Cell cycle analysis revealed that each of the Ca2+ ionophores inhibited tumor cell transition from the G1 phase to the S phase of the cell cycle and, possibly, arrested cells already in the S-phase. These data suggest that an early activation signal such as increased [Ca2+]i may initiate surface to nuclear signals that are different in normal T cells than in transformed cells that may receive opposite effects. Our studies suggest that non-specific activation of tumor cells by various stimuli may provide a useful approach to treat tumors in vivo.
Nagarkatti
M
M
Department of Biology, Virginia Polytechnic Institute, Blacksburg.
Nagarkatti
P S
PS
D000818:Animals; D000970:Antineoplastic Agents; D000001:Calcimycin / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D015759:Ionomycin / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000970:Antineoplastic Agents; D000001:Calcimycin; D015759:Ionomycin