Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: para- NO-ASA induced apoptosis in CLL cells with an LC(50) (lethal concentration) of 8.72 + 0.04 μmol/L, whereas healthy blood cells were not affected. Furthermore, the compound induced caspase 9, caspase 3, and PARP cleavage. In addition, cleavage of β- catenin and downregulation of β- catenin/ lymphoid enhancer factor (Lef)-1 targets was observed. para- NO-ASA demonstrated strong antitumor efficacy in the xenograft mouse model with a tumor inhibtion rate of 83.4%. During therapy, no gross toxicity could be observed. CONCLUSIONS: para- NO-ASA selectively induces apoptosis in primary CLL cells and efficiently reduces tumor growth in a CLL-like xenograft model. As NO-ASA is orally available and is generally well tolerated, para- NO-ASA might be a promising new compound for CLL therapy.
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Authors | Regina Razavi, Iris Gehrke, Rajesh Kumar Gandhirajan, Simon Jonas Poll-Wolbeck, Michael Hallek, Karl-Anton Kreuzer |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 17
Issue 2
Pg. 286-93
(Jan 15 2011)
ISSN: 1557-3265 [Electronic] United States |
PMID | 21097689
(Publication Type: Journal Article)
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Copyright | ©2010 AACR. |
Chemical References |
- Antineoplastic Agents
- LEF1 protein, human
- Lymphoid Enhancer-Binding Factor 1
- Nitric Oxide Donors
- beta Catenin
- Caspases
- Aspirin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Aspirin
(therapeutic use)
- Caspases
(biosynthesis)
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell
(drug therapy)
- Lymphoid Enhancer-Binding Factor 1
(metabolism)
- Mice
- Mice, Nude
- Nitric Oxide Donors
(therapeutic use)
- Xenograft Model Antitumor Assays
- beta Catenin
(metabolism)
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