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, Wayne State University School of MedicineFollow
Amro Aboukameel, Wayne State University School of MedicineFollow
Jianyong Chen, University of Michigan Comprehensive Cancer CenterFollow
Dajun Yang, Ascenta Therapeutics, Inc.Follow
Shaomeng Wang, University of Michigan Comprehensive Cancer CenterFollow
Ayad Al-Katib, Wayne State University School of MedicineFollow
Ramzi M. Mohammad, Wayne State University School of MedicineFollow

Document Type

Article

Abstract

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.

Disciplines

Oncology

Recommended Citation

Arnold et al. Molecular Cancer 2008, 7:20
doi:10.1186/1476-4598-7-20