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Lipid metabolism, apoptosis and cancer therapy.

Huang C, Freter C - Int J Mol Sci (2015)

Bottom Line: Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules.These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways.Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Internal Medicine, School of Medicine and Cancer Center, Saint Louis University, 3655 Vista Avenue, Saint Louis, MO 63110, USA. chunfahuang@slu.edu.

ABSTRACT
Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

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Related in: MedlinePlus

Glycerophospholipid metabolism. Left, glycerophospholipid synthesis; Right, glycerophospholipid degradation. The enzymes are choline kinase (ChoK), ethanolamine kinase (EthK), cytidine 5'-triphosphate (CTP)-phosphocholine (or phosphethanolamine) cytidylyltransferase (CCT), cholinephosphotransferase (CPT), ethanolaminephosphotransferase (EPT), phosphatidylethanolamine N-methyltransferase (PEMT), CDP-diacylglycerol synthase (CDS), phosphatidylglycerol synthase (PGS), phosphatidylserine synthase (PSS), phosphatidylserine decarboxylase (PSD), phosphatidylinositol synthase (PIS), phosphatidylinositol kinase (PIK), phosphatidylinositol phosphate kinase (PIPK), phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase B (PLB), phospholipase C (PLC), and phospholipase D (PLD). P-Cho, phosphocholine; P-Eth, phosphoethanolamine; CDP-Cho, CDP-choline; CDP-Eth, CDP-ethanolamine; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PS, phosphatidylserine; PI, phosphatidylinositol; PIP, phosphatidylinositol phosphate; PIP2, phosphatidylinositol bisphosphate; R1 and R2, acyl group; and Head groups are choline, inositol, serine, ethanolamine or glycerol.
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ijms-16-00924-f001: Glycerophospholipid metabolism. Left, glycerophospholipid synthesis; Right, glycerophospholipid degradation. The enzymes are choline kinase (ChoK), ethanolamine kinase (EthK), cytidine 5'-triphosphate (CTP)-phosphocholine (or phosphethanolamine) cytidylyltransferase (CCT), cholinephosphotransferase (CPT), ethanolaminephosphotransferase (EPT), phosphatidylethanolamine N-methyltransferase (PEMT), CDP-diacylglycerol synthase (CDS), phosphatidylglycerol synthase (PGS), phosphatidylserine synthase (PSS), phosphatidylserine decarboxylase (PSD), phosphatidylinositol synthase (PIS), phosphatidylinositol kinase (PIK), phosphatidylinositol phosphate kinase (PIPK), phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase B (PLB), phospholipase C (PLC), and phospholipase D (PLD). P-Cho, phosphocholine; P-Eth, phosphoethanolamine; CDP-Cho, CDP-choline; CDP-Eth, CDP-ethanolamine; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PS, phosphatidylserine; PI, phosphatidylinositol; PIP, phosphatidylinositol phosphate; PIP2, phosphatidylinositol bisphosphate; R1 and R2, acyl group; and Head groups are choline, inositol, serine, ethanolamine or glycerol.

Mentions: Glycerophospholipids are the main component of biological membranes and contain at least one O-1-acyl, O-1-alkyl, or O-1-alkenyl residue attached to the glycerol moiety. The presence of an additional head group (such as choline, ethanolamine, serine, inositol, and glycerol) attached to the phosphate allows for many different glycerophospholipids. Both biosynthesis (CDP-DAG pathway and Kennedy pathway) and degradation (different phospholipases) of glycerophospholipids are regulated by different signaling pathways (Figure 1). Interestingly, many different bioactive lipid molecules, such as inositol trisphosphate, diacylglycerol, arachidonic acid, phosphatidic acid, and lysophosphatidic acid, are generated during glycerophospholipid metabolism, and these bioactive lipid molecules in turn regulate different signaling pathways in the cells [12,13]. The metabolism of glycerophospholipids is very complex and it is not fully understood how and when their substitutions and modifications occur.


Lipid metabolism, apoptosis and cancer therapy.

Huang C, Freter C - Int J Mol Sci (2015)

Glycerophospholipid metabolism. Left, glycerophospholipid synthesis; Right, glycerophospholipid degradation. The enzymes are choline kinase (ChoK), ethanolamine kinase (EthK), cytidine 5'-triphosphate (CTP)-phosphocholine (or phosphethanolamine) cytidylyltransferase (CCT), cholinephosphotransferase (CPT), ethanolaminephosphotransferase (EPT), phosphatidylethanolamine N-methyltransferase (PEMT), CDP-diacylglycerol synthase (CDS), phosphatidylglycerol synthase (PGS), phosphatidylserine synthase (PSS), phosphatidylserine decarboxylase (PSD), phosphatidylinositol synthase (PIS), phosphatidylinositol kinase (PIK), phosphatidylinositol phosphate kinase (PIPK), phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase B (PLB), phospholipase C (PLC), and phospholipase D (PLD). P-Cho, phosphocholine; P-Eth, phosphoethanolamine; CDP-Cho, CDP-choline; CDP-Eth, CDP-ethanolamine; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PS, phosphatidylserine; PI, phosphatidylinositol; PIP, phosphatidylinositol phosphate; PIP2, phosphatidylinositol bisphosphate; R1 and R2, acyl group; and Head groups are choline, inositol, serine, ethanolamine or glycerol.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307283&req=5

ijms-16-00924-f001: Glycerophospholipid metabolism. Left, glycerophospholipid synthesis; Right, glycerophospholipid degradation. The enzymes are choline kinase (ChoK), ethanolamine kinase (EthK), cytidine 5'-triphosphate (CTP)-phosphocholine (or phosphethanolamine) cytidylyltransferase (CCT), cholinephosphotransferase (CPT), ethanolaminephosphotransferase (EPT), phosphatidylethanolamine N-methyltransferase (PEMT), CDP-diacylglycerol synthase (CDS), phosphatidylglycerol synthase (PGS), phosphatidylserine synthase (PSS), phosphatidylserine decarboxylase (PSD), phosphatidylinositol synthase (PIS), phosphatidylinositol kinase (PIK), phosphatidylinositol phosphate kinase (PIPK), phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase B (PLB), phospholipase C (PLC), and phospholipase D (PLD). P-Cho, phosphocholine; P-Eth, phosphoethanolamine; CDP-Cho, CDP-choline; CDP-Eth, CDP-ethanolamine; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PS, phosphatidylserine; PI, phosphatidylinositol; PIP, phosphatidylinositol phosphate; PIP2, phosphatidylinositol bisphosphate; R1 and R2, acyl group; and Head groups are choline, inositol, serine, ethanolamine or glycerol.
Mentions: Glycerophospholipids are the main component of biological membranes and contain at least one O-1-acyl, O-1-alkyl, or O-1-alkenyl residue attached to the glycerol moiety. The presence of an additional head group (such as choline, ethanolamine, serine, inositol, and glycerol) attached to the phosphate allows for many different glycerophospholipids. Both biosynthesis (CDP-DAG pathway and Kennedy pathway) and degradation (different phospholipases) of glycerophospholipids are regulated by different signaling pathways (Figure 1). Interestingly, many different bioactive lipid molecules, such as inositol trisphosphate, diacylglycerol, arachidonic acid, phosphatidic acid, and lysophosphatidic acid, are generated during glycerophospholipid metabolism, and these bioactive lipid molecules in turn regulate different signaling pathways in the cells [12,13]. The metabolism of glycerophospholipids is very complex and it is not fully understood how and when their substitutions and modifications occur.

Bottom Line: Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules.These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways.Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Internal Medicine, School of Medicine and Cancer Center, Saint Louis University, 3655 Vista Avenue, Saint Louis, MO 63110, USA. chunfahuang@slu.edu.

ABSTRACT
Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

Show MeSH
Related in: MedlinePlus