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Nakashima M.,Kitasato University | Nakashima M.,Laboratory of Tumor Cell Biology | Ishii Y.,Tokyo Medical University | Watanabe M.,Kitasato University | And 5 more authors.
Cancer Science | Year: 2010

Although disturbed cytokinesis of mononuclear Hodgkin (H) cells is thought to generate Reed-Sternberg (RS) cells, differentiation of Hodgkin's lymphoma (HL) cells is not fully understood. Recent studies indicate that cells found in a side population (SP) share characteristics of cancer stem cells. In this study we identified an SP in the HL cell lines, KMH2 and L428. This SP almost entirely consists of distinct small mononuclear cells, whereas the non-SP is a mixture of relatively large cells with H or RS cell-like morphology. Culture of the small mononuclear cells in the SP from KMH2 generated a non-SP. Single cell culture of the SP cells generated large cells with H or RS cell-like morphology. We found that CD30 overexpression and constitutive nuclear factor-κB (NF-κB) activity, both of which are characteristics of HL cells, are shared between the SP and non-SP cells for both KMH2 and L428. Inhibition of NF-κB induced apoptosis in both fractions, whereas the SP cells were resistant to a conventional chemotherapeutic agent doxorubicin. The results show that HL cell lines contain an SP, that is enriched for distinct small mononuclear cells and generates larger cells with H and RS cell-like morphology. The results also stress the significance of NF-κB inhibition for eradication of HL cells. (Cancer Sci 2010; 101: 2490-2496) © 2010 Japanese Cancer Association.

Togano T.,Kitasato University | Togano T.,Laboratory of Tumor Cell Biology | Nakashima M.,Kitasato University | Nakashima M.,Laboratory of Tumor Cell Biology | And 5 more authors.
Oncology Research | Year: 2013

Constitutive NF-kB activation characterizes a subset of myeloid leukemia (ML) cells. Recent reports have indicated that DNA methyltransferase (DNMT) inhibitors are alternative candidates for the treatment of ML. However, the optimal use of DNMT as a chemotherapeutic agent against ML has yet to be established. In this report, we examined the effect of the NF-kB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) and its combinational use with the DNMT inhibitor 5-azacytidine (AZA) in ML cell lines. DHMEQ alone induced cell death in ML cell lines with NF-kB activation, although the response varied among the cell lines. The addition of DHMEQ enhanced the effect of AZA on the viability and apoptosis induction of ML cell lines. The treatment of ML cell lines with AZA marginally induced NF-kB binding activity, although the treatment induced NF-kB protein. These results indicate the potential usefulness of DHMEQ and its combinational use with AZA in the treatment of ML, although the molecular effect by AZA on the NF-kB pathway awaits further study. Copyright © 2013 Cognizant Comm. Corp.

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