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Open Access 01-12-2008 | Research

Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-X_L and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model

Authors: Alan A Arnold, Amro Aboukameel, Jianyong Chen, Dajun Yang, Shaomeng Wang, Ayad Al-Katib, Ramzi M Mohammad

Published in: Molecular Cancer | Issue 1/2008

Abstract

Elevated expression of anti-apoptotic Bcl-2 family proteins have been linked to a poor survival rate of patients with Follicular Lymphoma (FL). This prompted us to evaluate a very potent non-peptidic Small-Molecule Inhibitor (SMI) targeting Bcl-2 family proteins, Apogossypolone (ApoG2) using follicular small cleaved cell lymphoma cell line (WSU-FSCCL) and cell isolated from lymphoma patients. ApoG2 inhibited the growth of WSU-FSCCL significantly with a 50% growth inhibition of cells (IC₅₀) of 109 nM and decreased cell number of fresh lymphoma cells. ApoG2 activated caspases-9, -3, and -8, and the cleavage of Poly (ADP-ribose) polymerase (PARP) and Apoptosis Inducing Factor (AIF). In the WSU-FSCCL-SCID xenograft model, ApoG2 showed a significant anti-lymphoma effect, with %ILS of 84% in the intravenous and 63% in intraperitoneal treated mice. These studies suggest that ApoG2 can be an effective therapeutic agent against FL.

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Title: Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-XL and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model
Authors: Alan A Arnold
Amro Aboukameel
Jianyong Chen
Dajun Yang
Shaomeng Wang
Ayad Al-Katib
Ramzi M Mohammad
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2008
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-7-20

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