Specific growth suppression of human cancer cells by targeted delivery of Dictyostelium mitochondrial ribosomal protein S4

Cancer Cell International

Yasuo Maeda³  Hikaru Araki¹  Junji Chida² 

[1] Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho, Tokushima 770-8503, Japan;Division of Molecular Neurobiology, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho, Tokushima 770-8503, Japan;Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan

关键词: Dictyostelium discoideum;    Human tumor;    Differentiation;    Proliferation;    Apoptosis;    Anticancer action;    Dd-mrp4;    Mitochondrial ribosomal protein S4 (MRP4);   

Others  :  791772
DOI  :  10.1186/1475-2867-14-56

 received in 2014-04-27, accepted in 2014-06-09,  发布年份 2014

【 摘 要 】

Background

In general, growth and differentiation are mutually exclusive but are cooperatively regulated throughout development. Thus, the process of a cell’s switching from growth to differentiation is of great importance not only for the development of organisms but also for malignant transformation, in which this process is reversed. We have previously demonstrated using a Dictyostelium model system that the Dictyostelium mitochondrial ribosomal protein S4 (Dd-mrp4) gene expression is essential for the initiation of cell differentiation: Dd-mrp4-null cells fail to initiate differentiation, while the initial step of cell differentiation and the subsequent morphogenesis are markedly enhanced in mrp4^OE cells overexpressing the Dd-mrp4 in the extramitochondrial cytoplasm. This raised a possibility that the ectopically enforced expression of the Dd-mrp4 in human cells might inhibit their growth, particularly of malignant tumor cells, by inducing cell differentiation.

Methods

Four kinds of human tumor cell lines were transfected by three kind of vector constructs (the empty vector: pcDNA3.1 (Mock); pcDNA3.1-rps4 bearing Dictyostelium cytoplasmic ribosomal protein S4; pcDNA3.1-mrp4 bearing Dictyostelium mitochondrial ribosomal protein S4). As controls, four kinds of human primary cultured cells were similarly transfected by the above vector constructs. After transfection, growth kinetics of cells was analyzed using cell viability assay, and also the TUNEL method was used for evaluation of apoptotic cells.

Results

Ectopically expressed Dd-mrp4 suppressed cell proliferation through inducing apoptotic cell death specifically in the human lung adenocarcinoma (A549), epithelial cervical cancer (HeLa), hepatocellular carcinoma (HepG2) and colonic carcinoma (Caco-2), but not in primary cultured normal cells, such as human brain microvascular endothelial cells (HBMECs); human umbilical vein endothelial cells (HUVECs) and human normal hepatocytes (hHeps™), with one exception (human cardiac fibloblasts (HCF)).

Conclusion

The present finding that the ectopically enforced expression of Dd-mrp4 in human several tumor cell lines specifically suppresses their proliferation suggests strongly that the Dd-mrp4 gene derived from Dictyostelium mitochondria may provide a new promising therapeutic strategy for disrupting cell viability pathways in human cancers.

【 授权许可】

   
2014 Chida et al.; licensee BioMed Central Ltd.

【 图 表 】

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