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

• Main Authors: Al-Katib Ayad, Wang Shaomeng, Yang Dajun, Chen Jianyong, Aboukameel Amro, Arnold Alan A, Mohammad Ramzi M
• Format: Article
• Language: English
• Published: BMC 2008-02-01
• Series: Molecular Cancer
• Online Access: http://www.molecular-cancer.com/content/7/1/20

<p>Abstract</p> <p>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.</p>