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Attenuated Leishmanial Sphingolipid Induces Apoptosis in A375 Human Melanoma Cell via Both Caspase-Dependent and -Independent Pathways

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Title Attenuated Leishmanial Sphingolipid Induces Apoptosis in A375 Human Melanoma Cell via Both Caspase-Dependent
and -Independent Pathways
 
Creator Ratha, Jagnyeswar
Majumdar, Kajal Nayan
Dhara, Koushik
Singh, Suman Kumar
Das Saha, Krishna
Bhadra, Ranjan
 
Subject Infectious Diseases and Immunology
 
Description A fraction of attenuated Leishmanial lipid
(ALL) rich in sphingolipids, previously shown to have
apoptosis inducing activity in mouse melanoma (B16F10)
and human melanoma (A375) cells, was resolved to isolate
the bioactive sphingolipid. The mechanism of apoptosis
induction by this bioactive attenuated Leishmanial sphingolipid
(ALSL) was studied in A375 cells. Apoptosis induced
by ALSL in A375 cells was found to be dose and
time-dependent. Exposure of cells to ALSL resulted in a
rapid increase in reactive oxygen species generation. Pretreatment
of cells with the antioxidant N-acetyl-cystein
reduced ROS generation and attenuated apoptosis induced
by ALSL. Again, ALSL sensitization resulted in the activation
of caspase-3 and -9 but not caspase-8. However,
inhibitors of these caspases could not protect the cells
completely from ALSL-induced apoptosis. N-acetylcystein
pretreatment was again found to attenuate the
activation of caspase-3 and -9. ALSL treatment also
resulted in the alteration of mitochondrial membrane potential, and release of pro-apoptotic factors such as
cytochrome c and apoptosis inducing factor (AIF) from
mitochondria. Furthermore, c-Jun N-terminal kinase was
activated that resulted in apoptosis of A375 cells, whereas
p38 MAPK was activated to counteract the stress generated
in cells in response to ALSL treatment. Taken together,
our results indicate that ALSL-induced apoptosis of A375
cells is mediated by both mitochondrial caspase-dependent
and -independent pathways and it involves ROS and JNK
activation in the mitogen-activated protein kinase cascade.
 
Date 2007
 
Type Article
PeerReviewed
 
Relation http://dx.doi.org/10.1007/s11010-007-9495-5
http://www.eprints.iicb.res.in/271/
 
Identifier Ratha, Jagnyeswar and Majumdar, Kajal Nayan and Dhara, Koushik and Singh, Suman Kumar and Das Saha, Krishna and Bhadra, Ranjan (2007) Attenuated Leishmanial Sphingolipid Induces Apoptosis in A375 Human Melanoma Cell via Both Caspase-Dependent and -Independent Pathways. Molecular and Cellular Biochemistry, 304 (1-2). pp. 143-154.