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

Alan A Arnold¹ , Amro Aboukameel¹ , Jianyong Chen² , Dajun Yang³ , Shaomeng Wang² , Ayad Al-Katib¹ and Ramzi M Mohammad¹

¹Department of Internal Medicine, Division of Hematology/Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA

²Department of Internal Medicine and Medicinal Chemistry, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA

³Ascenta Therapeutics, Inc., Malvern, Pennsylvania, USA

author email corresponding author email

Molecular Cancer 2008, 7:20doi:10.1186/1476-4598-7-20

Published:	14 February 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.