Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator.
J Inorg Biochem
; 146: 1-13, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25699476
ABSTRACT
Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)-NHC complexes (NHC=N-heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt (II) and respective Ag(I)-NHC complex (III) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II. Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organometálicos
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Apoptosis
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Inhibidores de la Ciclooxigenasa 2
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Macrófagos
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Antiinflamatorios
Límite:
Humans
Idioma:
En
Revista:
J Inorg Biochem
Año:
2015
Tipo del documento:
Article
País de afiliación:
Malasia