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Xanthohumol Induces Apoptosis in Human Malignant Glioblastoma Cells by Increasing Reactive Oxygen Species and Activating MAPK Pathways

Festa, Michela ; Capasso, Anna ; D’Acunto, Cosimo W ; Masullo, Milena ; Rossi, Adriano G ; Pizza, Cosimo ; Piacente, Sonia

Journal of natural products (Washington, D.C.), 2011-12, Vol.74 (12), p.2505-2513 [Periódico revisado por pares]

Northbrook, IL: American Chemical Society and American Society of Pharmacognosy

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Título:
Xanthohumol Induces Apoptosis in Human Malignant Glioblastoma Cells by Increasing Reactive Oxygen Species and Activating MAPK Pathways
Autor: Festa, Michela ; Capasso, Anna ; D’Acunto, Cosimo W ; Masullo, Milena ; Rossi, Adriano G ; Pizza, Cosimo ; Piacente, Sonia
Assuntos: Acetylcysteine - pharmacology ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Biological and medical sciences ; Caspase 3 - drug effects ; Caspase 3 - metabolism ; Caspase 9 - drug effects ; Caspase 9 - metabolism ; Cyclohexenes - chemistry ; Cyclohexenes - pharmacology ; Cytochromes c - metabolism ; Dose-Response Relationship, Drug ; Flavonoids - chemistry ; Flavonoids - pharmacology ; General pharmacology ; Glioblastoma - drug therapy ; Glioblastoma - metabolism ; Humans ; Imidazoles - pharmacology ; Italy ; Medical sciences ; Mitogen-Activated Protein Kinases - metabolism ; Molecular Structure ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Poly(ADP-ribose) Polymerases - drug effects ; Poly(ADP-ribose) Polymerases - metabolism ; Propiophenones - chemistry ; Propiophenones - pharmacology ; Pyridines - pharmacology ; Reactive Oxygen Species - analysis ; Reactive Oxygen Species - metabolism ; Terpenes - chemistry ; Terpenes - pharmacology
É parte de: Journal of natural products (Washington, D.C.), 2011-12, Vol.74 (12), p.2505-2513
Descrição: The effect of the biologically active prenylated chalcone and potential anticancer agent xanthohumol (1) has been investigated on apoptosis of the T98G human malignant glioblastoma cell line. Compound 1 decreased the viability of T98G cells by induction of apoptosis in a time- and concentration-dependent manner. Apoptosis induced by 1 was associated with activation of caspase-3, caspase-9, and PARP cleavage and was mediated by the mitochondrial pathway, as exemplified by mitochondrial depolarization, cytochrome c release, and downregulation of the antiapoptotic Bcl-2 protein. Xanthohumol induced intracellular reactive oxygen species (ROS), an effect that was reduced by pretreatment with the antioxidant N-acetyl-l-cysteine (NAC). Intracellular ROS production appeared essential for the activation of the mitochondrial pathway and induction of apoptosis after exposure to 1. Oxidative stress due to treatment with 1 was associated with MAPK activation, as determined by ERK1/2 and p38 phosphorylation. Phosphorylation of ERK1/2 and p38 was attenuated using NAC to inhibit ROS production. After treatment with 1, ROS provided a specific environment that resulted in MAPK-induced cell death, with this effect reduced by the ERK1/2 specific inhibitor PD98059 and partially inhibited by the p38 inhibitor SB203580. These findings suggest that xanthohumol (1) is a potential chemotherapeutic agent for the treatment of glioblastoma multiforme.
Editor: Northbrook, IL: American Chemical Society and American Society of Pharmacognosy
Idioma: Inglês

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Xanthohumol Induces Apoptosis in Human Malignant Glioblastoma Cells by Increasing Reactive Oxygen Species and Activating MAPK Pathways

Festa, Michela ; Capasso, Anna ; D’Acunto, Cosimo W ; Masullo, Milena ; Rossi, Adriano G ; Pizza, Cosimo ; Piacente, Sonia

Northbrook, IL: American Chemical Society and American Society of Pharmacognosy

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