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Blood, Vol. 113, Issue 4, 846-855, January 22, 2009
SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK
Blood Okawa et al.
113: 846
Supplemental materials for: Okawa et al
Files in this Data Supplement:
- Table S1. Comparison of anti-tumor effect between SNX-2112 and 17-AAG in Solid tumors (PDF, 52.0 KB) -
Various solid tumor cell lines were cultured with SNX-2112 or 17-AAG for 72 h, and cell growth was evaluated by Cyquant® cell proliferation assay. IC50 values represent mean ± SD of quadruplicate determinations.
- Table S2. Comparison of anti-tumor effect between SNX-2112 and 17-AAG in MM cell lines (PDF, 30.6 KB) -
IC50 of MM cell lines treated with SNX-2112 for 48 hours compared to 17-AAG. ND indicates not determined. Cell growth was assessed by MTT assay. Values represent mean ± SD of triplicate cultures.
- Table S3. Signaling cascade downregulated by SNX-2112 (PDF, 60 KB) -
PBMNCs were cultured with M-CSF and RANKL for indicated days, in the presence or absence of 10 nM SNX-2112. Cell lysates were subjected to Western blotting. Table shows relative intensity of each band in Fig. 5E, assessed by densitometry.
- Figure S1. SNX-2112 inhibits Akt and ERK pathways (JPG, 38.2 KB)
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MM.1S cells were cultured with SNX-2112 (0 or 250 nM), with or without IL-6 (10 ng/ml) or IGF-1 (50 ng/ml) for 12 hr. Cell lysates were subjected to western blotting.
- Figure S2. Cell viability of HUVEC treated with SNX-2112 (JPG, 20.4 KB)
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HUVEC were cultured with SNX-2112 for 24 hours at indicated doses. Cell viability was assessed by MTT assay. Values represent mean ± SD of triplicate cultures.
- Figure S3. SNX-5422 inhibits p-Akt in vivo (JPG, 68.8 KB)
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Tumors from mice treated with SNX-5422 were evaluated by immunohistochemical analysis for p-Akt. SNX-5422 significantly inhibits p-Akt in treated (40 mg/kg) compared with control mice.
- Figure S4. Hsp90 protein is more highly expressed in MM cells than normal cells (JPG, 37.1 KB)
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Cell lysates of MM cell lines (A), normal and MM cells (B), and MM patient cells (B; lane 4) were analyzed by immunoblotting. (A) lane 1,U266; lane 2,MM.1S; lane 3, MM.1R; lane 4,RPMI8226; lane 5,RPMI Dox40; lane 6,RPMI LR5; lane 7,OPM1; and lane 8,OPM2. (B) (lane 1-3, normal plasma cells; lane 4, patient MM cells; lane 5, MM.1S).
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