Inhibitory effects of cytokines on ovarian and endometrial carcinoma cells in vitro with special reference to induction of specific transcriptional regulators

: Seppanen M, Henttinen T, Lin L, Punnonen J, Grenman S, Punnonen R, Vihko KK

Publisher: COGNIZANT COMMUNICATION CORP

: 1998

Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics

ONCOLOGY RESEARCH

: ONCOL RES

: 10

: 11-12

: 575

: 589

: 15

: 0965-0407

In present study, we have investigated the effects of interferons-alpha (IFN-alpha) and -gamma (IFN-gamma), interleukin-10 (IL-10) and -13 (IL-13), transforming growth factor-beta 1 (TGF-beta(1)), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) on cell proliferation and induction of transcription factors AP-1 and NF-kappa B in UM-EC-3 human endometrial adenocarcinoma cells and UT-OC-5 ovarian carcinoma cells in vitro. In addition, cellular DNA was extracted to study if any of these factors is able to induce apoptosis. In UM-EC-3 cell line DNA synthesis was inhibited by GM-CSF, IL-10, IL-13, TGF-beta(1), IFN-alpha, and IFN-gamma after 48 and 72 h in culture, whereas TNF-alpha had no significant effect on cell proliferation in any of the experiments. The inhibition of DNA synthesis was similarly observed in UT-OC-5 ovarian carcinoma cells by IL-10, TNF-alpha, and IFN-gamma after 48 and 72 h, whereas IFN-alpha bad no statistically significant effect. An inhibitory effect of GM-CSF was observed only after 48 h and TGF-beta after 72 h in culture, respectively. Transcription factors AP-1 and NF-kappa B were both constitutively active in UM-EC-3 and UT-OC-5 cells. The binding activity of AP-1 was found to be stimulated by all growth-inhibitory cytokines studied in both cell lines, whereas the specific binding activity of NF-kappa B was affected moderately only by TNF-alpha in UT-OC-5 ovarian carcinoma cells. No signs of DNA fragmentation typical of apoptosis were observed in any of these studies.