Ardisiphenol D, a resorcinol derivative identified from Ardisia brevicaulis, exerts antitumor effect through inducing apoptosis in human non-small-cell lung cancer A549 cells.

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. 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. 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. 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. 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.