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Corchorusin-D Directed Apoptosis of K562 Cells Occurs through Activationof Mitochondrial and Death Receptor Pathways and Suppression of AKT/PKB Pathway

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Title Corchorusin-D Directed Apoptosis of K562 Cells Occurs through Activationof Mitochondrial and Death Receptor Pathways and Suppression of AKT/PKB Pathway
 
Creator Mallicka, Sumana
Pal, Bikas C
Vedasiromoni, Joseph R
Kumar, Deepak
Das Saha, Krishna
 
Subject Cancer Biology and Inflammatory Disorder Division
Chemistry
 
Description Saponins, plant glycosides, have been reported to possess anti-cancer properties. Therefore
the effect of corchorusin-D (COR-D), a compound isolated from Corchorus acutangulus, was
studied in the chronic myelogenous leukemic cell line K562, using MTT assay, phase contrast
and confocal microscopy, annexin V binding, cell cycle analysis and western blotting. COR-D
inhibited cell growth in K562 cells and showed increased number of Annexin V FITC binding
cells. Characteristic apoptotic changes, seen under phase contrast and confocal microscopes
with accumulation of cells in the sub-G0 phase. The apoptosis involved drop in Bcl-2/Bax
ratio, loss of mitochondrial membrane potential, release of cytochrome c in cytosol followed
by activation of caspases 9 and 3, and cleavage of PARP. Down-regulation of pro-caspase 10
was observed along with formation of death-inducing signaling complex between TNF-R1
and TRADD. COR-D suppressed PDK1 and AKT with activation of MAP kinase family members
ERK1/2, JNK1/2 and p38. Thus it induced apoptosis by activating mitochondrial and death
receptor pathways and suppressing AKT/PKB rather than MAP kinase pathway. Significant
enhancement of apoptosis, noted using specific inhibitors of ERK1/2, p38 and JNK1/2, suggests
that COR-D can enhance apoptosis in K562 cells in combination with MAP kinase inhibitors.
 
Publisher Karger
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1670/1/CELLULAR_PHYSIOLOGY_AND_BIOCHEMISTRY___30_(_4_)915%2D926_;2012[142].pdf
Mallicka, Sumana and Pal, Bikas C and Vedasiromoni, Joseph R and Kumar, Deepak and Das Saha, Krishna (2012) Corchorusin-D Directed Apoptosis of K562 Cells Occurs through Activationof Mitochondrial and Death Receptor Pathways and Suppression of AKT/PKB Pathway. Cellular Physiology and Biochemistry, 30 (4). pp. 915-926.
 
Relation http://dx.doi.org/10.1159/000341469
http://www.eprints.iicb.res.in/1670/