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  • Title: Ardisiphenol D, a resorcinol derivative identified from Ardisia brevicaulis, exerts antitumor effect through inducing apoptosis in human non-small-cell lung cancer A549 cells.
    Author: Zhao F, Hu Y, Chong C, Lu M, Chen L, Kan W, Chen L, Liu H.
    Journal: Pharm Biol; 2014 Jul; 52(7):797-803. PubMed ID: 24392814.
    Abstract:
    CONTEXT: The in vitro and in vivo antitumor activities of ardisiphenol D, a natural product isolated from the roots of Ardisa brevicaulis Diels (Myrsinaceae), have been studied. OBJECTIVE: Previously, we have isolated and identified some chemical constituents from this plant. Furthermore, these compounds showed significant inhibition of the proliferation of human pancreatic PANC-1, human lung A549, human gastrointestinal carcinoma SGC 7901, human breast MCF-7, and human prostate PC-3 cancer cells. In the present paper, a major resorcinol derivative called ardisiphenol D was further studied for its antitumor mechanism. MATERIALS AND METHODS: MTT assay was used to detect the proliferation of A549 cancer cells. Apoptosis induced by ardisiphenol D was observed by Hoechst 33258 fluorescence staining. Caspase-3 enzyme activity was measured by a commercial caspase-3 enzyme activity detection kit. Protein expression of bax, bcl-2, and caspase-3 was tested by Western blots. In vivo antitumor activity of ardisiphenol D was evaluated by determination of A549 tumor growth in nude mice. RESULTS: Ardisiphenol D significantly inhibited the proliferation of A549 cells with an IC50 of 0.997 μM with a 48 h treatment. Hoechst 33258 fluorescence staining results indicated the apoptosis of A549 cells induced by 3.125 μM of ardisiphenol D. About 0.39 and 0.78 μM of ardisiphenol D also potently increased the caspase-3 enzyme activity in 24 h. Furthermore, 0.39-3.125 μM of ardisiphenol D induced the activation of caspase-3 protein and the up-regulation of the ratio of bax/bcl-2 protein expression in A549 cells. After i.p. injection, ardisiphenol D (5 mg/kg) also strongly suppressed the A549 tumor growth in nude mice. DISCUSSION AND CONCLUSION: Ardisiphenol D induced apoptosis of A549 cells via activation of caspase-3 and up-regulation of the ratio of bax/bcl-2 protein expression. Ardisiphenol D also strongly suppressed the A549 tumor growth in nude mice and exerted antitumor activity in vivo.
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