Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs.

Growing evidence supports a link between inflammation and cancer; however, mediators of the transition between inflammation and carcinogenesis remain incompletely understood. Sphingosine-1-phosphate (S1P) lyase (SPL) irreversibly degrades the bioactive sphingolipid S1P and is highly expressed in enterocytes but downregulated in colon cancer. Here, we investigated the role of SPL in colitis-associated cancer (CAC).

Sphingosine phosphate lyase regulates myogenic differentiation via S1P receptor-mediated effects on myogenic microRNA expression.

S1P lyase (SPL) catalyzes the irreversible degradation of sphingosine-1-phosphate (S1P), a bioactive lipid whose signaling activities regulate muscle differentiation, homeostasis, and satellite cell (SC) activation. By regulating S1P levels, SPL also controls SC recruitment and muscle regeneration, representing a potential therapeutic target for muscular dystrophy. We found that SPL is induced during myoblast differentiation.

Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in immunity, inflammation, angiogenesis, and cancer. S1P lyase (SPL) is the essential enzyme responsible for S1P degradation. SPL augments apoptosis and is down-regulated in cancer.

S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes cardiomyocyte survival and contributes to ischemic preconditioning. S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism. We hypothesized that SPL contributes to oxidative stress by depleting S1P pools available for cardioprotective signaling.

Natural sphingadienes inhibit Akt-dependent signaling and prevent intestinal tumorigenesis.

Sphingolipid metabolites regulate cell proliferation, migration, and stress responses. Alterations in sphingolipid metabolism have been proposed to contribute to carcinogenesis, cancer progression, and drug resistance. We identified a family of natural sphingolipids called sphingadienes and investigated their effects in colon cancer.

Sphingosine 1-phosphate lyase enzyme assay using a BODIPY-labeled substrate.

Sphingosine 1-phosphate lyase (SPL) is responsible for the irreversible catabolism of sphingosine 1-phosphate, which signals through five membrane receptors to mediate cell stress responses, angiogenesis, and lymphocyte trafficking. The standard assay for SPL activity utilizes a radioactive dihydrosphingosine 1-phosphate substrate and is expensive and cumbersome. In this study, we describe an SPL assay that employs an omega-labeled BODIPY-sphingosine 1-phosphate substrate, allowing fluorescent product detection by HPLC and incorporating advantages of the BODIPY fluorophore.

A rapid fluorescence assay for sphingosine-1-phosphate lyase enzyme activity.

Sphingosine-1-phosphate (S1P) lyase (SPL) catalyzes the conversion of S1P to ethanolamine phosphate and hexadecenal. This enzyme plays diverse roles in physiology and disease and, thus, may be useful as a disease marker and/or drug target. Unfortunately, the radioisotope-based assay currently used to quantify SPL activity is suboptimal.

Sphingosine-1-phosphate lyase in immunity and cancer: silencing the siren.

Sphingosine-1-phosphate (S1P) is a bioactive lipid that promotes cell survival, proliferation and migration, platelet aggregation, mediates ischemic preconditioning, and is essential for angiogenesis and lymphocyte trafficking. Sphingosine-1-phosphate lyase (SPL) is the enzyme responsible for the irreversible degradation of S1P and is, thus, in a strategic position to regulate these same processes by removing available S1P signaling pools, that is, silencing the siren. In fact, recent studies have implicated SPL in the regulation of immunity, cancer surveillance and other physiological processes.

Redirection of sphingolipid metabolism toward de novo synthesis of ethanolamine in Leishmania.

In most eukaryotes, sphingolipids (SLs) are critical membrane components and signaling molecules. However, mutants of the trypanosomatid protozoan Leishmania lacking serine palmitoyltransferase (spt2-) and SLs grow well, although they are defective in stationary phase differentiation and virulence. Similar phenotypes were observed in sphingolipid (SL) mutant lacking the degradatory enzyme sphingosine 1-phosphate lyase (spl-).

Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer.

Sphingolipid metabolites such as sphingosine-1-phosphate (S1P) and ceramide modulate apoptosis during development and in response to stress. In general, ceramide promotes apoptosis, whereas S1P stimulates cell proliferation and protects against apoptosis. S1P is irreversibly degraded by the enzyme S1P lyase (SPL).

The immune modulator FTY720 inhibits sphingosine-1-phosphate lyase activity.

FTY720 is a novel immunomodulatory agent that inhibits lymphocyte trafficking and prevents allograft rejection. FTY720 is phosphorylated in vivo, and the phosphorylated drug acts as agonist for a family of G protein-coupled receptors that recognize sphingosine 1-phosphate. Evidence suggests that FTY720-phosphate-induced activation of S1P1 is responsible for its mechanism of action.

Roots of Withania somnifera Inhibit Forestomach and Skin Carcinogenesis in Mice.

We evaluated the cancer chemopreventive efficacy of the Withania somnifera root, which has been used in the Indian traditional medicine system for many centuries for the treatment of various ailments. Since, studies showing its mechanism-based cancer chemopreventive efficacy are limited, this was investigated in the present study. We studied the effect of dietary administration of Withania root on hepatic phase I, phase II and antioxidant enzymes by estimation of its level/activity, as well as in attenuating carcinogen-induced forestomach and skin tumorigenesis in the Swiss albino mouse model.

Chemoprevention by Hippophae rhamnoides: effects on tumorigenesis, phase II and antioxidant enzymes, and IRF-1 transcription factor.

Fruits or berries of Hippophae rhamnoides (sea buckthorn), a rich source of vitamins A, C, and E, carotenes, flavonoids, and microelements such as sulfur, selenium, zinc, and copper, are edible and have been shown to protect from atopic dermatitis, hepatic injury, cardiac disease, ulcer, and atherosclerosis. However, its mechanism of action is not clear. We show that Hippophae inhibits benzo(a)pyrene-induced forestomach and DMBA-induced skin papillomagenesis in mouse.