Novel dual-targeting anti-proliferative dihydrotriazine-chalcone derivatives display suppression of cancer cell invasion and inflammation by inhibiting the NF-κB signaling pathway
| Autor: | Wai Keung Chui, Muthukumar Karuppasamy, Eng-Hui Chew, Wei Hseun Yeap, Siew Cheng Wong, Ruirui Zhang, Waygene Seah, Hui-Li Ng, Eva Hadadi, Fei-Fei Gan, Siew-Min Ong |
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| Rok vydání: | 2018 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Chalcone Thioredoxin reductase Down-Regulation Nitric Oxide Synthase Type II Antineoplastic Agents Breast Neoplasms Enzyme-Linked Immunosorbent Assay Toxicology Monocytes Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Dihydrofolate reductase Animals Humans Neoplasm Invasiveness Cell Proliferation Inflammation biology Triazines Cell growth Chemistry NF-kappa B General Medicine Nitric oxide synthase RAW 264.7 Cells 030104 developmental biology Matrix Metalloproteinase 9 Cyclooxygenase 2 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein Tetradecanoylphorbol Acetate Tumor necrosis factor alpha Inflammation Mediators Signal transduction Signal Transduction Food Science |
| Zdroj: | Food and Chemical Toxicology. 116:238-248 |
| ISSN: | 0278-6915 |
| Popis: | Chalcones present in edible plants possess anti-cancer and anti-inflammatory properties, with the Michael acceptor moiety reported to be responsible for their biological activities. In this study, two novel dihydrotriazine-chalcone compounds previously identified to exert anti-proliferative effects through dual-targeting of dihydrofolate reductase (DHFR) and thioredoxin reductase (TrxR), were evaluated for their anti-invasive and anti-inflammatory abilities. At non-lethal concentrations, the compounds suppressed in vitro migration of MDA-MB-231 breast carcinoma cells, which was correlated with a dose-dependent downregulation of phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) expression and secretion. At similar concentrations, these chalcone-based compounds suppressed expression of inflammatory mediators inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharides (LPS)-stimulated murine macrophage-like RAW 264.7 cells, as well as tumor necrosis factor alpha (TNF-α) in LPS-stimulated human monocytes isolated from healthy donors. Mechanistically, inhibition of cancer cell invasion and inflammation by the compounds were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway, which corroborated with the reported mechanism of action of chalcones. Their abilities to target multiple biological mediators relevant to multi-step carcinogenesis and with bioactivities stronger than those of the parent chalcone scaffold have warranted dihydrotriazine-chalcone compounds as promising candidates for use in pharmacological intervention of aggressive cancers. |
| Databáze: | OpenAIRE |
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