Abstract | BACKGROUND: METHODS: Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β- catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta- NO-ASA, para- NO-ASA or vehicle control. RESULTS: The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para- NO-ASA acted in the low micromolar range. meta- NO-ASA, in contrast to para- NO-ASA, did not alter caspase activity. While para- NO-ASA action involved inhibition of β- catenin/Lef-1 signaling, meta- NO-ASA did not show any impact on this signaling pathway. Further, meta- NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para- NO-ASA was highly potent. CONCLUSION: We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA.
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Authors | Iris Gehrke, Regina Razavi, Simon Jonas Poll-Wolbeck, Albrecht Berkessel, Michael Hallek, Karl-Anton Kreuzer |
Journal | Therapeutic advances in hematology
(Ther Adv Hematol)
Vol. 2
Issue 5
Pg. 279-89
(Oct 2011)
ISSN: 2040-6207 [Print] England |
PMID | 23556096
(Publication Type: Journal Article)
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