Affiliations 

  • 1 The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia; The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
  • 2 EMAN Research and Testing Laboratory, The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia; The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
  • 3 The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia. Electronic address: rosenani@usm.my
  • 4 EMAN Research and Testing Laboratory, The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM Penang, Malaysia
  • 5 The School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
J. Inorg. Biochem., 2015 May;146:1-13.
PMID: 25699476 DOI: 10.1016/j.jinorgbio.2015.02.001

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.