Leishmanial sphingolipid induces apoptosis in Sarcoma 180 cancer cells through regulation of tumour growth via angiogenic switchover
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Sphingolipids are membrane and intracellular lipids that typically modulate cellular processes to cause cell death. Exogenous administration of sphingolipids may cause restriction of tumour growth and several alternative strategies are being used to control the cell growth. The microbes, their cellular component(s) or metabolites like DHA, EPA and also FTY720 have been employed as new therapeutic entities to regulate the disease condition. The therapeutic efficacy of lipids from Leishmania donovani in rheumatoid arthritis and also in sepsis condition associated with inflammatory diseases is well established. In this study, we explored the apoptotic effect of LSPL-1 (leishmanial sphingolipid-1) in Sarcoma 180 cells towards the regulation of tumour growth. The study using a panel of cancer cell lines revealed that LSPL-1 induces cell death in Sarcoma 180. The apoptotic changes were assessed by annexin exposure and DNA content analysis using flow cytometry. LSPL-1 appears to activate several pro- and anti-apoptotic molecules through reactive oxygen species (ROS) generation and also caspase activation, as determined by Western blot and ELISA analyses. Simultaneously, it may improve the survival rate of mice bearing tumour induced by Sarcoma 180 cells, with pathological changes. LSPL-1 may also suppress the cancer-associated inflammatory responses with the expression of matrix metalloproteinase having inhibitory role. It may regulate several angiogenic factors including VEGF, Ang-2 and CD34 in angiogenic events generated in Sarcoma 180 cell-induced tumour. These studies underline the significance of anti-neoplastic potential of LSPL-1 through apoptosis induction and abrogation of angiogenic responses in Sarcoma 180 cell-associated tumour.
KeywordSphingolipid Apoptosis Tumour Angiogenesis
The Council of Scientific and Industrial Research, India financially supported this work. The authors convey their sincerest thanks to the Director, Dr. Chitra Mandal of CSIR-Indian Institute of Chemical Biology for providing us the necessary support for this work. We extend our thanks to Dr. Suvendra Nath Bhattacharyya (Indian Institute of Chemical Biology) and Mr. Diptadeep Sarkar for their help in confocal laser-scanning microscopy and Dr S. N. Kabir and Anushila Gangopadhyay for flow cytometry. We are also indebted to Dr. Basudeb Achari and Dr. J. Rajan Vedasiromoni of our institute for critically reviewing the manuscript.
Conflicts of interest
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