title: Permethylated Anigopreissin A inhibits human hepatoma cell proliferation by mitochondria-induced apoptosis.
abstract: Anigopreissin A belongs to stilbene di- and oligomeric forms containing a benzofuran ring system whose biological activity is unknown. Recently, a completely protected Anigopreissin A - Permethylated Anigopreissin A - has been synthesized. We use MTT bioassay to assess Permethylated Anigopreissin A cytotoxicity in different human cell lines. Furthermore, fluorescence microscopy, caspase activity, real-time PCR and Western-blot methods are employed to evaluate apoptotic cell death pathway in liver cancer cells. Permethylated Anigopreissin A kills different types of human cancer cells but does not affect non-tumorigenic cells. The Permethylated Anigopreissin A concentration that causes 50% inhibition of liver tumor cells is 0.24μM. Hepatoma cells treated with Permethylated Anigopreissin A arrest their cell cycle in G1 phase. We also demonstrate that Permethylated Anigopreissin A-triggered cell death occurs by apoptosis. Decrease of the BCL2 expression levels, loss of the mitochondrial membrane potential, release of cytochrome c and increase of caspase 9 activity highlight a key role for mitochondria in Permethylated Anigopreissin A-induced apoptosis. Our study shows that Permethylated Anigopreissin A kills liver cancer cells through intrinsic apoptotic pathway.
authors.affiliation: Department of Science, University of Basilicata, viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Convertini
authors.affiliation: Department of Science, University of Basilicata, viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tramutola
authors.affiliation: Department of Biosciences, Biotechnology and Pharmacological Sciences, University of Bari, via Orabona 4, 70100 Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Iacobazzi
authors.affiliation: Department of Science, University of Basilicata, viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lupattelli
authors.affiliation: Department of Science, University of Basilicata, viale dell'Ateneo Lucano 10, 85100 Potenza, Italy. Electronic address: lucia.chiummiento@unibas.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Chiummiento
authors.affiliation: Department of Science, University of Basilicata, viale dell'Ateneo Lucano 10, 85100 Potenza, Italy. Electronic address: vittoria.infantino@unibas.it.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Infantino
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D008745:Methylation; D060888:Real-Time Polymerase Chain Reaction; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D013267:Stilbenes; C000601830:permethylated anigopreissin A
keywords: Anticancer drug; Apoptosis; Cell cycle; Intrinsic apoptotic pathway; Liver cancer cells; Permethylated Anigopreissin A