Interleukin-1 alpha differentially synchronizes estrogen-dependent and estrogen-independent human breast cancer cells in the G0/G1 phase of the cell cycle.
Direct in vitro effects of IL-1 alpha on cell cycle progression of the estrogen-responsive, MCF-7, and estrogen-unresponsive, MDA-231, human breast cancer cells were investigated by flow cytometry. IL-1 alpha, at nanomolar concentrations, caused the synchronization of MCF-7, but not MDA-231, cells in the G0/G1 phase of the cell cycle. The S phase of IL-1 treated MCF-7 cells was correspondingly decreased. The IL-1 induced synchronization of MCF-7 cells was observed in the dose range of 10(-11) M to 10(-7) M and was seen as early as 6 h after the start of treatment. Furthermore, these effects were shown to be sensitive to the weak estrogen, phenol red, since the IL-1-induced shifts in G0/G1 and S phases were markedly blunted in its presence. In cell proliferation experiments, the IL-1-induced synchronization of MCF-7 cells increased the cytotoxic efficacy of the chemotherapeutic drug, 5-fluorodeoxyuracil. These data demonstrate that IL-1 by arresting the estrogen-responsive human breast cancer cells, MCF-7, in the G0/G1-phase of the cell cycle can not only directly inhibit the growth of MCF-7 cells, but also increase the efficacy of FUDR.
Paciotti
G F
GF
University of Maryland, Department of Zoology, College Park 20742.
Tamarkin
L
L
D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005467:Floxuridine / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D012334:RNA, Neoplasm / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
D004273:DNA, Neoplasm; D004967:Estrogens; D007375:Interleukin-1; D012334:RNA, Neoplasm; D005467:Floxuridine