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Dibenzylbutane‐ and Butyrolactone‐type Lignans as Apoptosis Inducers in Human Hepatoma HuH‐7 Cells
Author(s) -
Mansoor Tayyab A.,
Ramalho Rita M.,
Rodrigues Cecília M. P.,
Ferreira MariaJosé U.
Publication year - 2012
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3629
Subject(s) - apoptosis , dna fragmentation , lignan , lactate dehydrogenase , viability assay , fragmentation (computing) , microbiology and biotechnology , chemistry , biology , inducer , biochemistry , programmed cell death , enzyme , stereochemistry , ecology , gene
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. Copyright © 2011 John Wiley & Sons, Ltd.