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The synthetic furanonaphthoquinone induces growth arrest, apoptosis and differentiation in a variety of leukaemias and multiple myeloma cells
Author(s) -
Desmond Julian C.,
Kawabata Hiroshi,
MuellerTidow Carsten,
Simamura Eriko,
Heber David,
Hirai KeiIchi,
Phillip Koeffler H.
Publication year - 2005
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.1365-2141.2005.05803.x
Subject(s) - multiple myeloma , apoptosis , cancer research , variety (cybernetics) , medicine , biology , genetics , computer science , artificial intelligence
Summary 2‐Methyl‐naphtho[2,3‐ b ]furan‐4,9‐dione (FNQ3), a synthetic analogue of the quinone kigelinone, has demonstrated a real potential for use in the treatment of a variety of solid tumours. Unlike other quinones, such as mitomycin‐C and adriamycin, the cytotoxicity of FNQ3 is often 10‐ to 14‐fold more potent towards the tumour cells than their normal counterparts. We report, for the first time, that the drug had activity against a broad spectrum of leukaemias and multiple myeloma cells. It decreased the growth of acute myeloid leukaemia (AML) and multiple myeloma cell lines in a dose‐dependent fashion (50% inhibitory concentration ≈1·25 μ g/ml against most of the leukaemia cell lines). This dose apparently initiated mitochondrial collapse as measured by depolarisation of the mitochondrial membrane. FNQ3 potentiated the differentiation of HL‐60 myeloid cells in the presence of either 1 α , 25(OH) 2 dihydroxyvitamin D 3 [1 α ,25(OH) 2 D 3 ] or all‐ trans ‐retinoic acid (ATRA). FNQ3 inhibited the proliferation of primary AML cells while inducing apoptosis. Eleven of 14 (79%) AML marrow samples had a prominent decrease in their clonogenic growth when cultured in the presence of the drug. In summary, this drug has growth inhibitory, apoptotic and differentiative effects against myeloid leukaemias and multiple myeloma cells. FNQ3 may represent a new therapeutic approach to these malignancies.