title: A sphingolipid rich lipid fraction isolated from attenuated Leishmania donovani promastigote induces apoptosis in mouse and human melanoma cells in vitro.
abstract: 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.
authors.affiliation: Cellular Biochemistry Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Jagnyeswar
authors.initials: J
authors.lastname: Ratha
authors.forename: Kajal Nayan
authors.initials: KN
authors.lastname: Majumdar
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Mandal
authors.forename: Rabindranath
authors.initials: R
authors.lastname: Bera
authors.forename: Chinmoy
authors.initials: C
authors.lastname: Sarkar
authors.forename: Bidisha
authors.initials: B
authors.lastname: Saha
authors.forename: Chitra
authors.initials: C
authors.lastname: Mandal
authors.forename: Krishna Das
authors.initials: KD
authors.lastname: Saha
authors.forename: Ranjan
authors.initials: R
authors.lastname: Bhadra
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007893:Leishmania donovani / Q000737:chemistry*; D008545:Melanoma / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D013107:Sphingolipids / Q000302:isolation & purification / Q000633:toxicity*; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D013107:Sphingolipids; D053148:Caspase 3