Cell cycle regulation of emodin through p53, p21, and cyclin D pathway in human lung adenocarcinoma A549 cells

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active ingredient from Chinese herbs (Pheum palmatum L.), has been showed to have diverse pharmacologic actions such as laxative, redox-regulation, anti-microbial, and anti-inflammation [1]. Recently, emodin has been reported to have the ability to suppress the proliferation of carcinoma cells including lung cancer cell [2]. However, the molecular mechanisms of emodin-mediated lung cancer regression have not yet been defined. We investigated the effects of emodin on the various cancer cell lines to clarify the cytotoxic action. After the treatment of A549 cell with emodin, the cytotoxicity of emodin on A549 cell was assayed by XTT and methylene blue methods, and we found the cytotoxic IC₅₀ is around 40µM. Through flow cytometry method, we found a G1 phase arrest phenomenon after 72h emodin (50µM) treatment and the cell percentage of the G0/G1 phase was increased from 47.4% to 64.1%. The expressions of cell cycle signal proteins (p53, p21, p27, and cyclin D) were determined by Western blotting assay simultaneously. The blotting show that p53 protein increase in emodin-treated A549 cell and the downstream products of p53 target gene (p21 and p27) were also promoted. Since cyclin D related G0/G1 phase transition, our data also indicated that the expression of cyclin D was decrease after 72h emodin addition. Emodin acted as a suppressor on the proliferation of A549 in a time- and dose-dependent way and caused an accumulation at G0/G1 phase of the cell cycle in 72h. The anti-proliferative effect of emodin caused significant G1 cell cycle arrest which may be through molecular p53, p21, p27, and cyclin D modulation.

References: 1. Srinivas, G., et al. (2007) Med Res Rev 27: 591–608.

2. Su, Y.T., et al. (2005) Biochem Pharmacol 70: 229–241.