Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), an anticancer agent, exerts an anti-inflammatory effect in activated human mast cells.
Inflamm Res
; 66(10): 871-879, 2017 Oct.
Article
in En
| MEDLINE
| ID: mdl-28616734
ABSTRACT
OBJECTIVE:
Inflammation has been closely associated with the development and progression of cancer. Previously, we reported that mast cells play a critical role in tumor growth. The purpose of this study is to investigate the anti-inflammatory effect of an anticancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), on an activated human mast cell line, in this case HMC-1 cells.METHODS:
We evaluated the effect and specific molecular mechanism of Dp44mT on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI) using HMC-1 cells.RESULTS:
Here, we demonstrated that Dp44mT significantly decreased the protein levels of hypoxia-inducible factor-1α and vascular endothelial growth factor without exposing activated HMC-1 cells to any cytotoxicity. In activated mast cells, Dp44mT mitigated the strong production and mRNA expression of inflammatory cytokines, in this case, interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and thymic stromal lymphopoietin, through a blockade of caspase-1 and nuclear factor-κB activities. Furthermore, phosphorylations of the mitogen-activated protein kinase family included in inflammatory signaling cascades were significantly inhibited by a Dp44mT treatment.CONCLUSIONS:
Overall, our results indicate that the anticancer agent Dp44mT has an anti-inflammatory effect and may be of therapeutic importance for the treatment of mast cell-mediated inflammatory diseases.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiosemicarbazones
/
Mast Cells
/
Anti-Inflammatory Agents
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Inflamm Res
Journal subject:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Year:
2017
Type:
Article