Cerulenin induces apoptosis via activation of caspase-independent pathway

(A) MM.1S cells were cultured for 24 h with Cerulenin at the indicated doses. Induction of apoptosis by Cerulenin was determined by Apo2·7 staining and flow-cytometric analysis. (B) MM.1S cells were cultured with Cerulenin (50 μmol/l) for the indicated times (left panel), and preincubated with or without Z-VAD-FMK (50 μmol/l) for 1 h prior to treatment with Cerulenin for 12 h at the indicated doses (right panel). Total cell lysates (20 μg /lane) were subjected to Western blotting using anti-caspase -8, -9, -3, PARP, and α-tubulin Abs. FL, CF indicate the full length and cleaved form, respectively. (C, D) MM.1S cells were treated with the indicated dose of Cerulenin for 24 h, with or without Z-VAD-FMK (25 μmol/l or 50 μmol/l) 1 h pretreatment. Cytotoxicity was determined by MTT assay (C). Values represent mean ± SD of quadruplicate cultures. The percentage of apoptotic cells was determined by flow-cytometric analysis for APO2·7 staining (D). (E) Mitochondrial proteins AIF and Endo G were released into the cytosolic fraction from mitochondria after Cerulenin (50 μmol/l) treatment in MM.1S cells. Total cell lysates (20 μg/lane) were subjected to Western blotting using anti-AIF, Endo G, VDAC and α-tubulin Abs.<p><b>Copyright information:</b></p><p>Taken from "Retraction: Fatty acid synthase is a novel therapeutic target in multiple myeloma"</p><p></p><p>British Journal of Haematology 2008;141(5):659-671.</p><p>Published online Jan 2008</p><p>PMCID:PMC2408665.</p><p>Journal compilation © 2008 Blackwell Publishing Ltd</p

Cerulenin overcomes the protective effects of IL-6, IGF-1 and BMSCs on MM cell growth

(A, B, C) MM.1S and U266 cells were cultured for 48 h with the indicated concentrations [0 μmol/l (□), 3·15 μmol/l () 6·25 μmol/l (), 12·5 μmol/l ()] of Cerulenin, in the presence or absence of IL-6 (1 or 10 ng/ml: A), IGF-1 (10 or 50 ng/ml: B), or BMSC (C). Cell growth was assessed by [H]-thymidine uptake. Cerulenin inhibits MM cell growth and overcomes the stimulating effect of IL-6 (A) or IGF-1 (B) ( < 0·05), and BMSC ( < 0·05) (C). Values represent mean ± SD of quadruplicate cultures.<p><b>Copyright information:</b></p><p>Taken from "Retraction: Fatty acid synthase is a novel therapeutic target in multiple myeloma"</p><p></p><p>British Journal of Haematology 2008;141(5):659-671.</p><p>Published online Jan 2008</p><p>PMCID:PMC2408665.</p><p>Journal compilation © 2008 Blackwell Publishing Ltd</p