Antiproliferative effects of interferon gamma in combination with alpha-difluoromethylornithine on human carcinoma cell cultures. 1994

M Klouche, and H Kirchner, and F Hölzel
Department of Physiological Chemistry, University of Hamburg, Germany.

The antiproliferative effects of human recombinant interferon gamma (IFN gamma) in combination with alpha-difluoromethylornithine (DFMO) or as single agents were assessed on human cell cultures derived from carcinomas of the breast (MCF-7), the ovary (EFO-27) or the kidneys (EGI-4). Results were obtained in proliferation assays by direct cell counting. The cell lines differed considerably in their sensitivities to the antiproliferative effect of IFN gamma as compared by the 50% inhibition doses of the growth (ID50). In contrast to the findings with IFN gamma, similar antiproliferative effects resulted from the application of comparable doses of DFMO. While IFN gamma induced cytotoxic effects in EGI-4 cells, DFMO produced only cytostatic actions in the cell lines analyzed. Synergistic growth inhibition resulted from the combined application of IFN gamma and DFMO in EFO-27 cell cultures. This finding was most pronounced after treatment with IFN gamma or DFMO doses below the respective ID50 values. However, antagonistic effects occurred in cells of the line EGI-4 after DFMO had been combined with IFN gamma at concentrations below the cytotoxic dose range. Within the sensitivity of our proliferation assay, no synergistic interactions were found in MCF-7 cell cultures. In the cell lines tested, no relation between the sensitivity for the single agents and the effectivity of the drug combination was identified. Despite promising synergistic effects in the moderately IFN gamma-sensitive ovarian carcinoma cell line EFO-27, the efficacy of the IFN gamma/DFMO combination was restrained by possible antagonistic effects as demonstrated in the highly IFN gamma-sensitive EGI-4 renal carcinoma cell cultures. We conclude that the differential interaction patterns in the cell cultures analyzed preclude general suggestions for clinical studies using IFN gamma and DFMO.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007680 Kidney Neoplasms Tumors or cancers of the KIDNEY. Cancer of Kidney,Kidney Cancer,Renal Cancer,Cancer of the Kidney,Neoplasms, Kidney,Renal Neoplasms,Cancer, Kidney,Cancer, Renal,Cancers, Kidney,Cancers, Renal,Kidney Cancers,Kidney Neoplasm,Neoplasm, Kidney,Neoplasm, Renal,Neoplasms, Renal,Renal Cancers,Renal Neoplasm
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005260 Female Females
D006131 Growth Inhibitors Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth ( Cell Growth Inhibitor,Cell Growth Inhibitors,Growth Inhibitor,Growth Inhibitor, Cell,Growth Inhibitors, Cell,Inhibitor, Cell Growth,Inhibitor, Growth,Inhibitors, Cell Growth,Inhibitors, Growth
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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