Furanodiene induces G2/M cell cycle arrest and apoptosis through MAPK signaling and mitochondria-caspase pathway in human hepatocellular carcinoma cells.
Furanodiene (C15H20O), a pure compound isolated from Traditional Chinese medicine, Curcuma wenyujin, named Ezhu in Chinese, which structure was determined on the basis of NMR, MS and UV spectrum. In this study, we attempted to characterize in detail the signaling cascades resulted from furanodiene-induced apoptosis in human hepatoma HepG2 cells. Furanodiene inhibited HepG2 cell growth by causing cell cycle arrest at G2/M and inducing apoptosis as evidenced by DNA fragmentation assay. We found that furanodiene induced mitochondrial transmembrane depolarization, release of mitochondrial cytochrome c, activation of caspases-3 and the cleavage of PARP. The furanodiene mediated mitochondria-caspase apoptotic pathway also involved activation of p38 and inhibition of ERK mitogen-activated protein kinase (MAPK) signaling. These results for the first time have identified the biological activity of furanodiene against HepG2 cells and provide rationales for further development of essential oil of Ezhu and its ingredients such as furanodiene on treatment of liver diseases.
Xiao
Yu
Y
Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, PR China.
Yang
Feng-Qing
FQ
Li
Shao-Ping
SP
Gao
Jian-Li
JL
Hu
Guang
G
Lao
Sin-Cheng
SC
Conceição
Emilia Leong
EL
Fung
Kwok-Pui
KP
Wangl
Yi-Tao
YT
Lee
Simon Ming-Yuen
SM
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; C442489:furanodiene; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases