Alantolactone induces activation of apoptosis in human hepatoma cells.
Alantolactone, a sesquiterpene lactone, possesses anti-inflammatory property. In this study, we provide evidence that it could be developed as a novel agent against human liver cancer. We observed that alantolactone treatment to HepG2, Bel-7402 and SMMC-7721 cells, human liver cancer cell lines resulted in a dose-dependent inhibition of cell growth. We selected HepG2 cell line as a test model system. Alantolactone treatment of HepG2 cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G2-M phase. This induction of apoptosis seems to be mediated via modulating the protein levels of Bcl-2 family and activation of caspases. Moreover, caspase-8 and Bid activation, loss of mitochondrial transmembrane potential and cytochrome c release suggest the existence of a cross-talk between the death receptor and the mitochondrial pathways. We also observed that alantolactone treatment of cells resulted in a dose-dependent decrease in NF- κB/p65. In addition, a significant and progressive increase in the level of p53 protein in alantolactone-treated cells was observed. Taken together, our data suggest that alantolactone could be developed as an agent against human liver cancer.
Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China.
Jia-Chuan
JC
Lei
Jian-Qing
JQ
Yu
Yan
Y
Yin
Yan-Wen
YW
Liu
Guo-Lin
GL
Zou
D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D053181:Caspase 8 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology*
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D007783:Lactones; D045787:Sesquiterpenes, Eudesmane; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053181:Caspase 8; C004363:alantolactone