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Abstract
Transcription factor NF-κB plays a central role in tumorogenesis and in different types of cancer, including Hodgkin's lymphoma. Previously, we described that ( − )-epicatechin (EC) inhibits PMA-induced NF-κB activation in Jurkat T cells. Therefore, we investigated the capacity of EC to inhibit NF-κB activation, the underlying mechanisms and the effects of EC on cell viability in Hodgkin's lymphoma cells. EC inhibited NF-κB–DNA binding activity in L-428 and KM-H2 cells. This inhibition was not associated with EC antioxidant activity, with changes in p65 phosphorylation or NF-κB nuclear translocation. Results suggest that EC acted inhibiting the binding of NF-κB to DNA. The combined treatment with EC and an inhibitor of NF-κB nuclear translocation (SN-50) caused an additive inhibitory effect on NF-κB activation. The partial cell viability decrease, under conditions that EC and SN-50 completely prevented NF-κB–DNA binding, indicates that the inhibition of other signaling pathways should be also targeted in the treatment of Hodgkin's lymphoma.
| Abbreviations | ||
| NF-κB | = | nuclear factor-κB |
| HD | = | Hodgkin's disease |
| H–RS cells | = | Hodgkin and multi nucleated Reed-Sternberg cells |
| TNF-α | = | tumor necrosis factor-α |
| EBV | = | Epstein-Barr virus |
| PMA | = | phorbol 12-myristate 13-acetate |
| EC | = | ( − )-epicatechin |
| RANTES | = | regulated on activation normal T cell expressed and secreted |
| LA | = | ( ± )-α lipoic acid |
| CAT | = | catalase |
| FBS | = | fetal bovine serum |
| EDTA | = | ethylenediamine tetraacetate |
| DTT | = | dithiothreitol |
| HEPES | = | 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid |
| PBS | = | phosphate-buffered saline |
| DCDHF | = | 5(or 6)-carboxy-2’7’-dichlorodihydrofluorescein diacetate |
| DCF | = | 2’7’-dichlorofluorescein |
| EMSA | = | electrophoretic mobility shift assay |
| EGCG | = | ( − )-epigallocatechin gallate |
| EBV | = | Epstein-Barr virus |
| LMP-1 | = | latent membrane protein-1 |
| TRAF | = | tumor necrosis factor receptor-associated factor |
| NIK | = | NF-κB inducing kinase |
| IKK | = | IκB kinase |
| NF-IL-6 | = | nuclear factor of IL-6 |
| IRF-3 | = | interferon regulatory factor-3 |
| RFLAT-1 | = | RANTES factor of late activated T lymphocytes-1 |
| Abbreviations | ||
| NF-κB | = | nuclear factor-κB |
| HD | = | Hodgkin's disease |
| H–RS cells | = | Hodgkin and multi nucleated Reed-Sternberg cells |
| TNF-α | = | tumor necrosis factor-α |
| EBV | = | Epstein-Barr virus |
| PMA | = | phorbol 12-myristate 13-acetate |
| EC | = | ( − )-epicatechin |
| RANTES | = | regulated on activation normal T cell expressed and secreted |
| LA | = | ( ± )-α lipoic acid |
| CAT | = | catalase |
| FBS | = | fetal bovine serum |
| EDTA | = | ethylenediamine tetraacetate |
| DTT | = | dithiothreitol |
| HEPES | = | 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid |
| PBS | = | phosphate-buffered saline |
| DCDHF | = | 5(or 6)-carboxy-2’7’-dichlorodihydrofluorescein diacetate |
| DCF | = | 2’7’-dichlorofluorescein |
| EMSA | = | electrophoretic mobility shift assay |
| EGCG | = | ( − )-epigallocatechin gallate |
| EBV | = | Epstein-Barr virus |
| LMP-1 | = | latent membrane protein-1 |
| TRAF | = | tumor necrosis factor receptor-associated factor |
| NIK | = | NF-κB inducing kinase |
| IKK | = | IκB kinase |
| NF-IL-6 | = | nuclear factor of IL-6 |
| IRF-3 | = | interferon regulatory factor-3 |
| RFLAT-1 | = | RANTES factor of late activated T lymphocytes-1 |