and Differentiation of

The aims of this study were to isolate sesquiterpene compounds from the largehead atractylodes rhizome (LAR) and to investigate their effects on B16 cancer cells. A total of 8 sesquiterpenes from LAR were identified, of which eudesm-4 (15), 7-diene-9a, 11-diol (7) was isolated for the first time. All 8 compounds inhibited growth of B16 cells, and atractyleno-lide I (AT-I), atractylenolide II (AT-II), and atractylenolactam (ATR) were the most potent, with IC50 values of 76.46, 84.02, and 54.88 mΜ, respectively. Monomer lactone or lactam structures in the 8 compounds appeared to be critical for their antiproliferative activities. In addition, AT-I, AT-II, and ATR could induce cell differentiation and inhibit cell migration. Western blot analysis indicated that 2 of the compounds, AT-I and AT-II, could inactivate ERK, where all 3 inhibited AKT activation, suggesting that Ras/ERK and PI3K/AKT signaling pathways are involved in the action mechanisms of the LAR sesquiterpene compounds