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  • Title: N-Benzoyl-12-nitrodehydroabietylamine-7-one, a novel dehydroabietylamine derivative, induces apoptosis and inhibits proliferation in HepG2 cells.
    Author: Lin LY, Bao YL, Chen Y, Sun LG, Yang XG, Liu B, Lin ZX, Zhang YW, Yu CL, Wu Y, Li YX.
    Journal: Chem Biol Interact; 2012 Aug 30; 199(2):63-73. PubMed ID: 22743618.
    Abstract:
    The high biological activity of dehydroabietylamine derivatives has been reported previously. In this study, we aimed to screen 73 dehydroabietylamine derivatives as potential candidate inhibitors in liver cancer cells. Initially, the compounds structural activity relationship analysis was explored and N-benzoyl-12-nitrodehydroabietylamine-7-one (compound 81) was shown to have significant growth inhibitory activity in the human liver carcinoma cell line, HepG2. Further research into the anti-proliferative effect on HepG2 cells mediated by compound 81 was undertaken. The results suggest that compound 81 effectively induced apoptosis in HepG2 cells characterized by nuclear staining of DAPI, TUNEL assay and the activation of caspase-3. A decreased level of anti-apoptotic protein Bcl-2 and increased apoptotic Bax were also observed. Furthermore, Ki-67 protein staining and the BrdU incorporation assay showed that compound 81 significantly inhibited the proliferation of HepG2 cells. Cell cycle components analysis found that expression of cyclin D1 and cyclin B1 was reduced in HepG2 cells with compound 81 treatment, whereas the content of p21(Waf1/Cip1) was increased. Taken together, our data indicate that compound 81 induces apoptosis and inhibits proliferation in HepG2 cells, and may be a promising candidate in the development of a novel class of antitumor agents.
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