Effects of sesquiterpenes isolated from largehead atractylodes rhizome on growth, migration, and differentiation of B16 melanoma cells.
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-9α, 11-diol (7) was isolated for the first time. All 8 compounds inhibited growth of B16 cells, and atractylenolide I (AT-I), atractylenolide II (AT-II), and atractylenolactam (ATR) were the most potent, with IC(50) values of 76.46, 84.02, and 54.88 μΜ, 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.
Yan Ye
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Zhangjiang, Shanghai, China.
Chou
Gui-Xin
GX
Hui Wang
Chu
Jian-Hong
JH
Fong
Wang-fun
WF
Yu
Zhi-Ling
ZL
D000818:Animals; D031174:Atractylodes / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D028321:Plant Preparations; D027343:Rhizome / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007769:Lactams; D007783:Lactones; D010936:Plant Extracts; D028321:Plant Preparations; D012717:Sesquiterpenes; C424804:atractylenolide I; C458582:atractylenolide II; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases