Dexamethasone and suramin inhibit cell proliferation and interleukin-6-mediated immunoglobulin secretion in human lymphoid and multiple myeloma cell lines.
Uncontrolled growth of neoplastic cells and unregulated production of immunoglobulin are major components of the morbidity and mortality of multiple myeloma. Suramin, a polysulfonated napthylurea, has antitumor activity in a number of malignancies, but also significant dose-related toxicity. Suramin has been reported to have major antiproliferative effects in a variety of lymphoid cell lines. Glucocorticoids have long been recognized to have activity in lymphoid malignancies and multiple myeloma while IL-6 has been reported to be an autocrine growth factor for multiple myeloma. This study examines growth inhibition and inhibition of IL-6-mediated secretion of immunoglobulin in human lymphoid and myeloma cell lines by dexamethasone and suramin. Dexamethasone and suramin show synergistic inhibition of cell proliferation at their IC10 concentrations. IL-6-mediated immunoglobulin secretion is also inhibited by both dexamethasone and suramin in an additive fashion. Both dexamethasone and suramin induce apoptosis of lymphoid cell lines, and suramin inhibits the binding of IL-6 to its receptor in a multiple myeloma cell line. These findings suggest that the synergistic growth inhibitory activities of dexamethasone and suramin may be related to induction of apoptosis by both agents and inhibition of IL-6-mediated autocrine growth stimulation and immunoglobulin production. These results indicate that the combination of low-dose suramin (in concentrations not associated with significant clinical toxicity) and dexamethasone merit further study in the treatment of myeloma or lymphoid malignancies.
Shiao
R T
RT
Division of Medical Oncology, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Miglietta
L
L
Khera
S Y
SY
Wolfson
A
A
Freter
C E
CE
D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism*; D009101:Multiple Myeloma / Q000188:drug therapy*; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D013498:Suramin / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D015703:Antigens, CD; D004247:DNA; D003907:Dexamethasone; D007136:Immunoglobulins; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D013498:Suramin; D000093242:Interleukin-6 Inhibitors