Derivatives of monoglycerides as apoptotic agents in T-cells

Abstract

Recently, lipids have received considerable attention for their potential to induce apoptosis when added exogenously to cells. In this study, we directly demonstrate that murine T-cells undergo rapid apoptosis following treatment with various forms of monoglycerides, which are a family of naturally occurring lipids consisting of a single fatty acid moiety attached to a glycerol backbone. The potency of these lipids varied depending on their chemical structure, whereas glycerol backbone or corresponding fatty acids alone were ineffective. Moreover, monoglyceride-mediated apoptosis was suppressed either by Bcl-2 overexpression, treatment with a broad inhibitor of caspases, or RNA and protein synthesis inhibitors. In addition, treatment of cells with derivatives of monoglycerides induced a calcium flux, which could be inhibited by both extracellular (EGTA) or intracellular (EGTA-AM) calcium chelators. To our knowledge, this is the first report demonstrating a role for derivatives of monoglycerides as inducers of apoptosis in mammalian cells. Cell Death and Differentiation (2001) 8, 1103 ± 1112.

SWATH Differential Abundance Proteomics and Cellular Assays Show In Vitro Anticancer Activity of Arachidonic Acid- and Docosahexaenoic Acid-Based Monoacylglycerols in HT-29 Colorectal Cancer Cells

“…Free FA (FFA) and sn-2-monoacylglycerol (sn-2 MAG), the two hydrolysis products of dietary TAG, are absorbed from the lumen into polarized enterocytes in the small intestine. Polyunsaturated FAs (PUFAs) are better absorbed when they are esterified at the sn-2 position of the glycerol molecule, while the type of FA at the remaining locations also influences their intestinal absorption [2][3][4][5].…”

Monoglycerides induce apoptosis in human leukemic cells while sparing normal peripheral blood mononuclear cells

“…We have shown that monoglycerides induce apoptosis in murine cells 5 and wanted to examine the cytotoxicity of monoglycerides on malignant and normal human cells. We first evaluated the death-inducing potential of monoglycerides in a panel of human leukemic cell lines ( Figure 1A).…”

“…As described previously, 5,12 assays for apoptosis were the following: loosening of membrane phospholipids, measured with merocyanin-540 (MC540; Molecular Probes, Eugene, OR); phosphatidylserine exposure, assayed by FITCor biotin-conjugated annexin V followed by Quantum Red-conjugated streptavidin (BD BioSciences); retention of vital dyes, detected with propidium iodide (PI; Sigma-Aldrich); and DNA degradation, measured with the TdT-dependent dUTP-biotin nick end-labeling (TUNEL) assay.…”

“…Nonadherent and adherent cell lines were plated at 8 ϫ 10 5 /mL and 4 ϫ 10 5 /mL in RPMI-5% FCS, respectively. The agents used were glycerol, oleic acid, 1-monooleoyl-glycerol (1-C18:1), 1-monopalmitoleyl-glycerol (1-C16:1), and 3-monopalmitoyl-glycerol (3-C16:0), which were purchased and prepared as previously described, 5 and N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk; Kamiya Biomedical, Seattle, WA). Unless specified, "monoglycerides" refers to 1-C18:1 monoglyceride.…”

“…We have demonstrated that several monoglycerides induced rapid dose-dependent apoptosis in murine cells. 5 Thus, the objective of this work was to evaluate the death-inducing potential of monoglycerides on neoplastic and normal human cells. Using 1-C18:1 monoglyceride as a prototype, we provide evidence that monoglycerides can trigger death in various human leukemic cell lines.…”