Apoptosis induction and cell cycle arrest induced by Sinkiangenone B, a novel phenylpropanoid derivative from the resin of Ferula sinkiangensis K. M. Shen

Abstract

Four new phenylpropanoid derivatives, Sinkiangenone A–D (1–2, 4–5), together with eleven known compounds (3, 6–15), were isolated from the resin of Ferula sinkiangensis. Their structures were determined on the basis of spectroscopic analysis, including IR, UV, HR-ESI-MS, 1D NMR, 2D NMR and CD spectra. Of all the compounds, Sinkiangenone B showed the best antitumor activity against AGS gastric cancer cells with lower toxicity against normal human gastric epithelial cells. In addition, we characterized its mechanism of the antiproliferation effects on AGS cells. Annexin V-FITC/PI staining and increased Bax/Bcl-2 ratios indicated that Sinkiangenone B induced apoptosis in AGS cells. Cell cycle analysis showed Sinkiangenone B arrested cell cycle at G0/G1 phase. Western blot results showed the expression of P16, P27 and RB proteins increased, while the expression of P53, Cdk2, Cdk4, cyclin D1 and cyclin E decreased in AGS cells. In summary, these results suggested that Sinkiangenone B had the potential to be treated as a valuable candidate in gastric cancer therapy.