ZGDHu-1 promotes apoptosis of chronic lymphocytic leukemia cells

Qiu,Lian-Nv; Zhou,Yong-Lie; Wang,Zhen-Ni; Huang,Qiang; Hu,Wei-Xiao

doi:10.3892/ijo.2012.1467

ZGDHu-1 promotes apoptosis of chronic lymphocytic leukemia cells

Authors:
- Lian-Nv Qiu
- Yong-Lie Zhou
- Zhen-Ni Wang
- Qiang Huang
- Wei-Xiao Hu
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Affiliations: Centre of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou 310014, P.R. China, Centre of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou 310014, P.R. China, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, P.R. China
Published online on: May 8, 2012 https://doi.org/10.3892/ijo.2012.1467
Pages: 533-540

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Abstract

Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable with conventional modalities of chemotherapy. We aimed to examine the proapoptotic effects of a novel proteasome inhibitor, N,N'-di-(m-methylphenyi)-3,6- dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), on CLL cells. B lymphocytes were isolated from CLL patients and normal healthy controls, and treated with various concentrations of ZGDHu-1 for different days. CLL cell viability was detected by MTT assay. The apoptosis, mitochondrial membrane potential (∆ψm) and reactive oxidative species (ROS) were examined by flow cytometry. The expression of caspase-3 and Bcl-2/Bax ratio was detected by western blotting. ZGDHu-1 significantly reduced the viability of CLL cells and induced apoptosis in comparison to the control cells (both P<0.05). Normal peripheral B cells were resistant to the apoptosis-inducing effects of ZGDHu-1. Apoptosis induced by ZGDHu-1 was accompanied with generation of ROS, loss of ∆ψm, downregulation of Bcl-2 and increase of caspase-3 cleavage. Results of this study indicate that ZGDHu-1 is a promising specific treatment for CLL in the clinic.

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