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FQPD, a novel immunomodulatory drug, has significant in vitro activity in multiple myeloma
Author(s) -
Kumar Shaji,
Raje Noopur,
Hideshima Teru,
Ishitsuka Kenji,
Podar Klaus,
Gouille Steven Le,
Chauhan Dharminder,
Richardson Paul,
Munshi Nikhil C.,
Anderson Kenneth
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05946.x
Subject(s) - apoptosis , multiple myeloma , in vivo , in vitro , stromal cell , pharmacology , cancer research , cell culture , cytotoxicity , medicine , in vitro toxicology , bone marrow , immunology , chemistry , biology , biochemistry , genetics , microbiology and biotechnology
Summary Multiple myeloma (MM) is a plasma cell malignancy that claims thousands of lives each year and has considerable morbidity. The disease remains incurable despite recent advances in the understanding of the disease biology and the introduction of more effective drugs is needed. This study evaluated the anti‐MM activity of 3‐(7‐fluoro‐4H‐quinazolin‐3‐yl)‐piperidine‐2,6‐dione, hydrochloride (FQPD), a novel immunomodulatory drug. FQPD inhibited the proliferation of multiple MM cell lines, including those resistant to conventional treatments, such as dexamethasone. It induced apoptosis in MM cell lines, as well as freshly isolated patient MM cells, without cytotoxicity on normal human lymphocytes. Moreover, it induced apoptosis in MM cells adherent to bone marrow (BM) stromal cells or in the presence of cytokines, such as interleukin‐6 and vascular endothelial growth factor, confirming its ability to overcome the protective effects of the BM milieu. Apoptosis in the MM cells was mediated via poly‐ADP ribose polymerase cleavage as well as cleavage of caspase 8 and caspase 9. Our studies therefore demonstrated in vitro anti‐MM activity of FQPD and provide the rationale for its in vivo evaluation in animal models and derived clinical trials.