TY - JOUR
T1 - A sphingolipid rich lipid fraction isolated from attenuated Leishmania donovani promastigote induces apoptosis in mouse and human melanoma cells in vitro
AU - Ratha, Jagnyeswar
AU - Majumdar, Kajal Nayan
AU - Mandal, Sushil Kumar
AU - Bera, Rabindranath
AU - Sarkar, Chinmoy
AU - Saha, Bidisha
AU - Mandal, Chitra
AU - Saha, Krishna Das
AU - Bhadra, Ranjan
N1 - Funding Information:
We would like to thank Dr. Santu Bandopadhyay for providing instrumental assistance for FACS analysis. We are indebted to Dr. Basudev Achari of our institute for critically reviewing the manuscript. We also thank our Director, Prof. Siddhartha Roy for his patronization and keen interest in this work. Financial assistance from the CSIR (Council of Scientific and Industrial Research) and DBT (Department of Biotechnology), INDIA is thankfully acknowledged.
PY - 2006/10
Y1 - 2006/10
N2 - Lipids, especially sphingolipids, are emerging as inducer of apoptosis in a wide range of immortal cells, potentiating their therapeutic application in cancer. In the present study, a sphingolipid rich lipid fraction (denoted here as ALL), isolated from an attenuated strain of Leishmania donovani promastigote, was tested for its tumoricidal activity taking melanoma, the dreaded form of skin cancer cells, as model. ALL was found to induce chromatin condensation, internucleosomal DNA fragmentation and phosphatidylserine externalization with enhanced cell population in sub-G1 region in both mouse and human melanoma systems, namely B16F10 and A375 respectively. These are the hallmarks of cells undergoing apoptosis. Further analysis demonstrated that ALL treated melanoma cells showed significant increase in ROS generation, mitochondrial membrane potential depolarization, release of cytochrome c, and caspase-3 activation, which are the events closely involved in apoptosis. These findings indicate that one or more bioactive sphingolipid(s)/ceramide(s) present in ALL could be the causative agent(s) for the induction of apoptosis in melanoma cells. Further studies are thus necessary to identify these specific bioactive sphingolipid(s)/ceramide(s) and to establish their mechanism of action, in order to explore their use as anticancer agents.
AB - Lipids, especially sphingolipids, are emerging as inducer of apoptosis in a wide range of immortal cells, potentiating their therapeutic application in cancer. In the present study, a sphingolipid rich lipid fraction (denoted here as ALL), isolated from an attenuated strain of Leishmania donovani promastigote, was tested for its tumoricidal activity taking melanoma, the dreaded form of skin cancer cells, as model. ALL was found to induce chromatin condensation, internucleosomal DNA fragmentation and phosphatidylserine externalization with enhanced cell population in sub-G1 region in both mouse and human melanoma systems, namely B16F10 and A375 respectively. These are the hallmarks of cells undergoing apoptosis. Further analysis demonstrated that ALL treated melanoma cells showed significant increase in ROS generation, mitochondrial membrane potential depolarization, release of cytochrome c, and caspase-3 activation, which are the events closely involved in apoptosis. These findings indicate that one or more bioactive sphingolipid(s)/ceramide(s) present in ALL could be the causative agent(s) for the induction of apoptosis in melanoma cells. Further studies are thus necessary to identify these specific bioactive sphingolipid(s)/ceramide(s) and to establish their mechanism of action, in order to explore their use as anticancer agents.
KW - Apoptosis
KW - Attenuated Leishmania
KW - Melanoma
KW - Sphingolipid(s)
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U2 - 10.1007/s11010-006-9174-y
DO - 10.1007/s11010-006-9174-y
M3 - Article
C2 - 16718368
AN - SCOPUS:33749179836
SN - 0300-8177
VL - 290
SP - 113
EP - 123
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -