Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents.
We used a novel high-throughput drug screening assay, based on Luminex technology, to identify anti-myeloma agents capable of inhibiting cytokines and growth factors essential for multiple myeloma (MM) from a chemical library of 1120 compounds provided by MMRF. Tetracycline derivatives inhibited MM cell proliferation and osteoclast activating factors without obvious effect on cell viability. Steroid compounds specifically decreased angiogenesis-related factors, but stimulated osteoclast activating factors. Antihelmintic drugs potently inhibited cytokines and were cytotoxic. The screen identified potential candidates with potent anti-MM properties that need further investigation.
Feng
Rentian
R
Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
Rios
Jorge A
JA
Onishi
Tomifumi
T
Lokshin
Anna
A
Gorelik
Elieser
E
Lentzsch
Suzanne
S
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000871:Anthelmintics / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002301:Cardiac Glycosides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008863:Microspheres; D009101:Multiple Myeloma / Q000188:drug therapy*; D010010:Osteoclasts / Q000166:cytology
D000305:Adrenal Cortex Hormones; D000871:Anthelmintics; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D002301:Cardiac Glycosides; D016207:Cytokines; D006131:Growth Inhibitors