Antiproliferative and antitumor activity of the 2-cyanoaziridine compound imexon on tumor cell lines and fresh tumor cells in vitro

Evan M Hersh, Charles R. Gschwind, Charles W. Taylor, Robert T Dorr, Raymond Taetle, Sydney E. Salmon

Research output: Contribution to journalArticle

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Abstract

Background: Imexon, a 2-cyanoaziridine, is therapeutic and reverses lymphadenopathy and splenomegaly in the LP-BM5 murine retrovirus-induced immunodeficiency disease (murine AIDS). It can restore chemotherapy-induced immunosuppression. Imexon reduced the incidence of lymphoma in severe combined immune deficient mice inoculated with human lymphocytes. Purpose: To determine its antitumor activity, we screened imexon against fresh human tumor cells and tumor cell lines. To determine the time - concentration relationships of its cytotoxicity, we studied the effects of imexon on macromolecular synthesis and on the cell cycle. Methods: Imexon was incubated at 1-200 μg/mL with various tumor cell lines, mitogen-stimulated peripheral blood lymphocytes, and fresh tumor cells. Cell survival, macromolecular synthesis, and cell cycle progression were studied. Results: The concentration of imexon that caused 50% inhibition of growth was under 10 μg/mL for lymphocytes stimulated with mitogens. It was about 3-10 μg/mL for B-cell lymphomas and both multidrug-resistant and -sensitive myeloma cell lines. Imexon inhibited four of seven fresh lymphoma and 11 of 16 fresh myeloma biopsy specimens to less than 40% of the control. A 1-hour exposure of lymphoma cells to 50-100 μg/mL followed by removal of drug by washing the cells and continuing culture resulted in greater than 95% inhibition during the next 48-72 hours. Imexon selectively inhibited protein synthesis during the first 24-48 hours of exposure of lymphoma and myeloma cells. Cells exposed to inhibitory concentrations of imexon were blocked in cell cycle progression. Conclusion: Imexon may be a potentially useful agent in the treatment of malignant disease, particularly lymphoid malignancies, and should be explored further.

Original languageEnglish (US)
Pages (from-to)1238-1244
Number of pages7
JournalJournal of the National Cancer Institute
Volume84
Issue number16
StatePublished - Aug 19 1992

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Tumor Cell Line
Tumors
Tumor
Cells
Line
Cell
Neoplasms
Lymphocytes
Lymphoma
Cell Cycle
Mitogens
Progression
Murine Acquired Immunodeficiency Syndrome
4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
In Vitro Techniques
Cell line
Synthesis
Cytotoxicity
Chemotherapy
B Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Antiproliferative and antitumor activity of the 2-cyanoaziridine compound imexon on tumor cell lines and fresh tumor cells in vitro. / Hersh, Evan M; Gschwind, Charles R.; Taylor, Charles W.; Dorr, Robert T; Taetle, Raymond; Salmon, Sydney E.

In: Journal of the National Cancer Institute, Vol. 84, No. 16, 19.08.1992, p. 1238-1244.

Research output: Contribution to journalArticle

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abstract = "Background: Imexon, a 2-cyanoaziridine, is therapeutic and reverses lymphadenopathy and splenomegaly in the LP-BM5 murine retrovirus-induced immunodeficiency disease (murine AIDS). It can restore chemotherapy-induced immunosuppression. Imexon reduced the incidence of lymphoma in severe combined immune deficient mice inoculated with human lymphocytes. Purpose: To determine its antitumor activity, we screened imexon against fresh human tumor cells and tumor cell lines. To determine the time - concentration relationships of its cytotoxicity, we studied the effects of imexon on macromolecular synthesis and on the cell cycle. Methods: Imexon was incubated at 1-200 μg/mL with various tumor cell lines, mitogen-stimulated peripheral blood lymphocytes, and fresh tumor cells. Cell survival, macromolecular synthesis, and cell cycle progression were studied. Results: The concentration of imexon that caused 50{\%} inhibition of growth was under 10 μg/mL for lymphocytes stimulated with mitogens. It was about 3-10 μg/mL for B-cell lymphomas and both multidrug-resistant and -sensitive myeloma cell lines. Imexon inhibited four of seven fresh lymphoma and 11 of 16 fresh myeloma biopsy specimens to less than 40{\%} of the control. A 1-hour exposure of lymphoma cells to 50-100 μg/mL followed by removal of drug by washing the cells and continuing culture resulted in greater than 95{\%} inhibition during the next 48-72 hours. Imexon selectively inhibited protein synthesis during the first 24-48 hours of exposure of lymphoma and myeloma cells. Cells exposed to inhibitory concentrations of imexon were blocked in cell cycle progression. Conclusion: Imexon may be a potentially useful agent in the treatment of malignant disease, particularly lymphoid malignancies, and should be explored further.",
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AU - Gschwind, Charles R.

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AU - Salmon, Sydney E.

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N2 - Background: Imexon, a 2-cyanoaziridine, is therapeutic and reverses lymphadenopathy and splenomegaly in the LP-BM5 murine retrovirus-induced immunodeficiency disease (murine AIDS). It can restore chemotherapy-induced immunosuppression. Imexon reduced the incidence of lymphoma in severe combined immune deficient mice inoculated with human lymphocytes. Purpose: To determine its antitumor activity, we screened imexon against fresh human tumor cells and tumor cell lines. To determine the time - concentration relationships of its cytotoxicity, we studied the effects of imexon on macromolecular synthesis and on the cell cycle. Methods: Imexon was incubated at 1-200 μg/mL with various tumor cell lines, mitogen-stimulated peripheral blood lymphocytes, and fresh tumor cells. Cell survival, macromolecular synthesis, and cell cycle progression were studied. Results: The concentration of imexon that caused 50% inhibition of growth was under 10 μg/mL for lymphocytes stimulated with mitogens. It was about 3-10 μg/mL for B-cell lymphomas and both multidrug-resistant and -sensitive myeloma cell lines. Imexon inhibited four of seven fresh lymphoma and 11 of 16 fresh myeloma biopsy specimens to less than 40% of the control. A 1-hour exposure of lymphoma cells to 50-100 μg/mL followed by removal of drug by washing the cells and continuing culture resulted in greater than 95% inhibition during the next 48-72 hours. Imexon selectively inhibited protein synthesis during the first 24-48 hours of exposure of lymphoma and myeloma cells. Cells exposed to inhibitory concentrations of imexon were blocked in cell cycle progression. Conclusion: Imexon may be a potentially useful agent in the treatment of malignant disease, particularly lymphoid malignancies, and should be explored further.

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