Alantolactone induces activation of apoptosis in human hepatoma cells. 2012

Jia-Chuan Lei, and Jian-Qing Yu, and Yan Yin, and Yan-Wen Liu, and Guo-Lin Zou
Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China.

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.

UI MeSH Term Description Entries
D007783 Lactones Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES. Lactone
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D011065 Poly(ADP-ribose) Polymerases Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE. ADP-Ribosyltransferase (Polymerizing),Poly ADP Ribose Polymerase,Poly(ADP-Ribose) Synthase,Poly(ADP-ribose) Polymerase,PARP Polymerase,Poly ADP Ribose Transferase,Poly ADP-Ribose Synthase,Poly(ADP-Ribose) Transferase,Poly(ADPR) Polymerase,Poly(ADPribose) Polymerase,Poly ADP Ribose Synthase,Polymerase, PARP,Synthase, Poly ADP-Ribose
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006528 Carcinoma, Hepatocellular A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested. Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045304 Cytochromes c Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV. Cytochrome c,Ferricytochrome c,Ferrocytochrome c,Apocytochrome C
D045787 Sesquiterpenes, Eudesmane SESQUITERPENES cyclized into two adjoining cyclohexane rings but with a different configuration from the ARTEMISININS. Eudesmane Derivatives,Eudesmanes,Furanoeremophilane Derivatives,Furanoeremophilanes,Furanoeudesmane Derivatives,Furanoeudesmanes,Derivatives, Eudesmane,Derivatives, Furanoeremophilane,Derivatives, Furanoeudesmane,Eudesmane Sesquiterpenes
D051023 BH3 Interacting Domain Death Agonist Protein A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage. Bid Protein,tBid Protein,Truncated Bid Protein

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