Attenuated Leishmanial Sphingolipid Induces Apoptosis in A375 Human Melanoma Cell Via Both Caspase-Dependent and -independent pathways
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Attenuated Leishmanial Sphingolipid Induces Apoptosis in A375 Human Melanoma Cell Via Both Caspase-Dependent
and -independent pathways
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| Creator |
Ratha, Jagnyeswar
Majumdar, Kajal Nayan Dhara, Koushik Singh, Suman Kumar Das Saha, Krishna Bhadra, Ranjan |
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| Subject |
Cell Biology & Physiology
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| 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.
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| Date |
2007
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/270/1/MOLECULAR_AND_CELLULAR_BIOCHEMISTRY%2C_304(1%2D2)%2C143%2D154%2C2007[31].pdf
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. Mol Cell Biochem, 304 (1-2). pp. 143-154. |
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| Relation |
http://dx.doi.org/10.1007/s11010-007-9495-5
http://www.eprints.iicb.res.in/270/ |
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