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Preclinical studies of S1 in K562 cell line and primary chronic myeloid leukemia cells shown synergistic effect with Cytosine Arabinoside Hydrochloride

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6 Author(s)
WenJuan Chen ; Cancer Center, The First Hospital of JiLin University/ Shaanxi Provincial, Tumor Hospital, Changchun/ XI'AN, China ; ZhiChao Zhang ; Wei Han ; ChangJi Yuan
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Purpose: Overexpression of Bcl-2 protein has been observed in most of chronic myeloid leukemia (CML), especially in aggressive and blastic phases. The aim of this study is to investigate its therapeutic potential as a novel small-molecule inhibitor of Bcl-2 for the treatment of CML. Experimental Design: S1 is a new class of potent small-molecule inhibitor acting on Bcl-2 protein. The activity of S1 was evaluated in cultured Human chronic myeloid leukemia cell line K562 and patient CML samples, Drug combination therapy using S1 with a commonly used leukemia drug was also investigated. Results: K562 cells were exposed to various concentrations of S1 for 6h, MTT experiments showed that S1 inhibit proliferation on dose-dependent manner. S1 blocked K562cells in the G1 phase of cell cycle .S1 showed a synergistic effect when combined with Cytosine Arabinoside Hydrochloride (Ara-c) in inducing K562 cell apoptosis. Furthermore, S1 down-regulated the Bcl-2 protein in K562 cell line and primary CML cells. Conclusions: These studies show substantial induce apoptosis activity of S1 as a potent Bcl-2 inhibitor, demonstrate a synergistic combination effect, and suggest a rationale for future clinical trials.

Published in:

2010 3rd International Conference on Biomedical Engineering and Informatics  (Volume:2 )

Date of Conference:

16-18 Oct. 2010