Molecular Cancer (Feb 2008)

Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-X<sub>L </sub>and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model

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

DOI
https://doi.org/10.1186/1476-4598-7-20
Journal volume & issue
Vol. 7, no. 1
p. 20

Abstract

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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.