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Effects of diheptyldiselenide (DDS) on human tumor cell lines and on peripheral blood mononuclear cells
L Tentori1, S P Prete, R Pepponi
1Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Abstract:
In vitro effects of graded concentrations of diheptyldiselenide (DDS) on human tumor cell proliferation, and on the proliferative responses and immunological functions of peripheral blood mononuclear cells (MNC) were investigated. The agent significantly decreased tumor cell proliferation in a dose and time dependent manner. Proliferative responses of MNC to phytohemagglutinin (PHA) and interleukin-2 (IL-2) were also significantly depressed when MNCs were exposed to DDS (250 microM for 18 h) led to a significant increase in NK activity only in MNC samples showing very limited baseline NK function. On the other hand, generation of LAK cells was significantly inhibited by DDS. However, when the agent was added to the effector and target cell mixture during the 4 h 51Cr release cytotoxicity assay, no influence was found on NK and LAK-mediated target cell lysis. These studies show that high concentrations of DDS inhibit tumor cell proliferation and could also impair certain proliferative-dependent immune functions, without directly affecting cell-mediated cytolytic activity of effector cells.
Insights
Diheptyldiselenide (DDS) inhibits human tumor cell proliferation in vitro. While DDS impairs some immune cell functions, it does not directly affect the cell-mediated killing activity of natural killer (NK) and lymphokine-activated killer (LAK) cells.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Diheptyldiselenide (DDS) is an organoselenium compound with potential therapeutic applications.
- Understanding the immunomodulatory and anti-proliferative effects of DDS is crucial for its development.
Purpose of the Study:
- To investigate the in vitro effects of diheptyldiselenide (DDS) on human tumor cell proliferation.
- To evaluate the impact of DDS on the proliferative responses and immunological functions of peripheral blood mononuclear cells (MNC).
Main Methods:
- Human tumor cell lines and peripheral blood mononuclear cells (MNC) were treated with graded concentrations of DDS in vitro.
- Tumor cell proliferation was assessed using standard assays.
- MNC proliferation in response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) was measured.
- Natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell generation were evaluated.
- Cytotoxicity assays were performed to assess NK and LAK cell-mediated lysis.
Main Results:
- DDS significantly decreased human tumor cell proliferation in a dose- and time-dependent manner.
- DDS significantly depressed MNC proliferative responses to PHA and IL-2.
- DDS increased NK activity in MNC with low baseline function but inhibited LAK cell generation.
- DDS did not affect NK or LAK cell-mediated target cell lysis when added during the cytotoxicity assay.
Conclusions:
- High concentrations of DDS inhibit human tumor cell proliferation in vitro.
- DDS can impair certain immune functions, particularly those dependent on cell proliferation.
- DDS does not directly interfere with the cytolytic activity of effector cells like NK and LAK cells.