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Corchorusin-D, a Saikosaponin-like Compound Isolated from Corchorus Acutangulus Lam., Targets Mitochondrial Apoptotic Pathways in Leukemic Cell Lines (HL-60 and U937)

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Title Corchorusin-D, a Saikosaponin-like Compound Isolated from
Corchorus Acutangulus Lam., Targets Mitochondrial Apoptotic
Pathways in Leukemic Cell Lines (HL-60 and U937)
 
Creator Mallick, Sumana
Ghosh, Papiya
Samanta, Suman K
Kinra, Sumita
Pal, Bikas C
Gomes, Aparna
Vedasiromoni, J R
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description Purpose The presence of triterpene saponins in Corchorus
acutangulus Lam. has been reported. However, no
studies concerning biological activity of the plant extracts
have been done so far. In the present study, the anti-leukemic
activity of the methanol extract of aerial parts (ME)
of C. acutangulus has been investigated, and efforts have
been made to identify the active ingredient responsible for
this activity.
Methods The anti-leukemic activity of ME, its fractions
and corchorusin-D (COR-D), the active ingredient, was
investigated in leukemic cell lines U937 and HL-60 using
cell viability and MTT assays. The molecular pathways
leading to the activity of COR-D were examined by confocal microscopy, flow-cytometry, caspase and Western
blot assays.
Results ME, its n-butanolic fraction and COR-D inhibited
cell growth and produced significant cytotoxicity in leukemic
cell lines U937 and HL-60. COR-D produced
apoptotic cell death via mitochondrial disfunction and was
found to pursue the intrinsic pathway by inciting the
release of apoptosis-inducing factors (AIFs) from mitochondria.
COR-D-induced translocation of Bax from
cytosol to mitochondria facilitating caspase-9 activation
and up regulation of downstream pathways leading to
caspase-3 activation and PARP cleavage, which resulted in
the subsequent accumulation of cells in the sub-G0 phase
followed by DNA fragmentation.
Conclusions COR-D possesses significant anti-leukemic
activity in U937 and HL-60 cell lines by acting on the mitochondrial
apoptotic pathways. Since the necrotic body formation
is low after COR-D treatment, the occurrence of
inflammation in in vivo systems could be reduced, which represents
a positive indication in view of therapeutic application
 
Date 2010
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/56/1/CANCER_CHEMOTHERAPY_AND_PHARMACOLOGY__66(4)709%2D719;2010[36].pdf
Mallick, Sumana and Ghosh, Papiya and Samanta, Suman K and Kinra, Sumita and Pal, Bikas C and Gomes, Aparna and Vedasiromoni, J R (2010) Corchorusin-D, a Saikosaponin-like Compound Isolated from Corchorus Acutangulus Lam., Targets Mitochondrial Apoptotic Pathways in Leukemic Cell Lines (HL-60 and U937). Cancer Chemotherapy Pharmacology, 66 (4). pp. 709-719.
 
Relation http://dx.doi.org/10.1007/s00280-009-1214-3
http://www.eprints.iicb.res.in/56/