Leishmanial sphingolipid induces apoptosis in Sarcoma 180 cancer cells through regulation of tumour growth via angiogenic switchover

Abstract

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.

DHA Attenuates Hypoxia/Reoxygenation Injury by Activating SSeCKS in Human Cerebrovascular Pericytes

“…Further studies have shown that DHA can alleviate cerebral ischemia/reperfusion injury, maintain blood-brain barrier integrity, and reduce blood-brain barrier permeability [5]. Das S et al reported that DHA can inhibit the expression of VEGF and its receptor, Flk-1, through the VEGF pathway, thereby significantly inhibiting corneal neovascularization and tumor vascular growth [12]. On the other hand, eicosapentaenoic acid could effectively reduce the level of Ang-2 in the plasma of chronic diabetic patients [39].…”

“…DHA may be a promising drug for the treatment of cerebral ischemia/reperfusion injury [11]. Studies have reported that DHA can inhibit the expression of VEGF and its receptor, Flk-1, through the VEGF pathway to significantly inhibit the growth of corneal neovascularization and tumor blood vessels [12]. Recent studies have shown that DHA reduced apoptosis in rat brain microvascular endothelial cells induced by an underlying oxygen and glucose deprivation environment, thus decreasing Ang-2 and VEGF synthesis [13].…”

A novel enemy of cancer: recent investigations into protozoan anti-tumor properties

“…Sphingomyelin, a lipid found in cell membranes and intracellular regions, plays a crucial role in regulating cellular processes such as proliferation, differentiation, and apoptosis ( Maceyka and Spiegel, 2014 ). After treating Sarcoma 180 cells with Leishmania sphingomyelin in vitro , reactive oxygen species production and caspase activation were regulated, resulting in up-regulation of pro-apoptotic molecules (Bad, Bax and P53) and down-regulation of anti-apoptotic molecules (Bcl-2 and PARP) ( Das et al., 2015b ). This treatment also inhibited the production of pro-angiogenic factors such as VEGF, CD34, and Ang-2, affecting the cell division cycle and thus impacting tumor growth ( Das et al., 2015a ).…”

Macrophage as the Game Changer of the (Future) Therapeutic Paradigm

“…Regarding melanoma destruction by apoptosis is an unique feature of Leishmania sphingolipids as there is no convenient way destined to eliminate these skin cancer cells. Intracutaneous injection starting from a very small dose, one can attempt to treat melanoma through apoptosis induction [24,25].…”