Exposure to the anti-TNF-alpha drug thalidomide induces apoptotic cell death in human T leukemic cells.
TNF-alpha is a pro-inflammatory cytokine that plays a key role in disorders due to HIV-1 infection and replication such as Kaposi sarcoma, wasting, aphthous ulcerations and progression to AIDS. The controversial drug thalidomide is anti-inflammatory, anti-angiogenic and a selective inhibitor of TNF-alpha that is being studied as a treatment for HIV-1-related disorders, immune disorders and cancer. The cellular and molecular mechanism of thalidomide is unclear despite renewed clinical interest in the drug. Previous data from this laboratory indicate that thalidomide decreases cell growth and cell-cell interactions of human T leukemic cells. The specific aim of the present study is to determine whether thalidomide administration induces cell death via apoptosis. Low dose thalidomide treatment of human T leukemic cells exhibited rapid increases in caspase-3 activity, annexin V-FITC binding and DNA disintegration that is characteristic of apoptosis. These data indicate that low doses of thalidomide signal human T leukemic cells to die by apoptosis, which is a possible method of altering inflammatory cells and inflammatory activities.
Ezell
T N
TN
Cellular Immunology Laboratory, Department of Biology, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA.
Maloney
N
N
Githua
J W
JW
Taylor
L D
LD
D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000473:pathology; D013792:Thalidomide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases