title: Dibenzylbutane- and butyrolactone-type lignans as apoptosis inducers in human hepatoma HuH-7 cells.
abstract: Seven lignans, previously isolated from Pycnanthus angolensis or obtained by derivatization, namely the dibenzylbutane-type lignans threo-4,4'-dihydroxy-3-methoxylignan (1), 4'-hydroxy-3,3',4-trimethoxylignan (2), (-)-dihydroguaiaretic acid (3), 3,3',4,4'-tetramethoxylignan (4), 4,4'-diacetyl-3,3'-dimethoxylignan (5), heliobuphthalmin (6) and the butyrolactone lignan hinokinin (7), were evaluted for their ability as apoptosis inducers in human hepatoma HuH-7 cells. Cell viability assays, morphological evaluation of apoptosis and enzymatic analyses of caspase activity in HuH-7 cells were carried out. Using the lactate dehydrogenase lactate dehydrogenase (LDH) assay, it was demonstrated that the lignans (1-7) tested significantly reduced viability of HuH-7 cells. Morphologic evaluation of HuH-7 cells using Hoechst staining and fluorescence microscopy revealed that lignans 1-7 were strong inducers of apoptosis. In fact, HuH-7 cells developed morphological changes of apoptosis, including chromatin condensation, nuclear fragmentation and formation of apoptotic bodies. However, lignans 2 and 7 were the most promising compounds in this study, inducing 2.4- and 2.5-fold increases in apoptotic cells as compared to controls. Caspase-3-like activity assays confirmed the morphologic data.
authors: Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
authors: Tayyab A
authors: TA
authors: Mansoor
authors: Rita M
authors: RM
authors: Ramalho
authors: Cecília M P
authors: CM
authors: Rodrigues
authors: Maria-José U
authors: MJ
authors: Ferreira
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D052117:Benzodioxoles; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004149:Dioxoles / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D026324:Myristicaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: C583732:4'-hydroxy-3,3',4-trimethoxylignan; D000972:Antineoplastic Agents, Phytogenic; D051033:Apoptosis Inducing Factor; D052117:Benzodioxoles; D004149:Dioxoles; D007783:Lactones; D017705:Lignans; D010936:Plant Extracts; C475934:hinokinin; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D015107:4-Butyrolactone