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Induction of apoptosis by a synergistic lignan composition from Cedrus deodara in human cancer cells
Author(s) -
Sharma Parduman R.,
Shanmugavel M.,
Saxena Ajit K.,
Qazi Ghulam N.
Publication year - 2008
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.2511
Subject(s) - viability assay , apoptosis , trypan blue , programmed cell death , biology , comet assay , microbiology and biotechnology , genotoxicity , micronucleus test , chemistry , dna damage , biochemistry , toxicity , dna , organic chemistry
AP9‐cd, a synergistic lignan mixture from Cedrus deodara (Pinaceae) consisting of (−)‐wikstromal, (−)‐matairesinol and dibenzyl butyrolactol, depicted cytotoxic effects against numerous human cancer cell lines reported previously. The aim of this study was to investigate the mechanism of cell death in human cancer cells. The viability, morphological and ultrastructural changes in Molt‐4 cells were investigated. Using the trypan blue exclusion assay, we demonstrated that AP9‐cd significantly reduced the viability of Molt‐4 cells in a time‐ and dose‐dependent manner. Apoptotic assays using light microscopy revealed that this agent induced Molt‐4 cell apoptosis at varied concentrations. The treatment causes a loss in cell viability by activating the apoptotic process as identified by light and electron microscopy. The morphological changes of intracellular organelles in Molt‐4 cells treated with 30 µg/ml of AP9‐cd revealed the disruption of mitochondrial cristae. Other features included the vacuolization, chromatin condensation and formation of micronuclei. Surface ultrastructural studies of four different tumor cell lines (Molt‐4, HL‐60, PC‐3 and A‐549) treated with AP9‐cd depicted loss of surface projections, condensation and formation of apoptotic bodies. AP9‐cd treatment to transgenic fruit fly, Drosophila , carrying human adenomatous polpyposis coli (hAPC) gene enhanced eye phenotypes and therefore may inhibit Wnt/Wg pathway which is important in the aetiology of a number of human cancers. Copyright © 2008 John Wiley & Sons, Ltd.