Lipid Metabolism, Apoptosis and Cancer Therapy

Huang, Changcheng; Freter, Carl E.

doi:10.3390/ijms16010924

Cited by 354 publications

(260 citation statements)

References 174 publications

(223 reference statements)

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“…PEs are generated from the Kennedy pathway and CDP-DAG pathway [31]. It has been demonstrated that PEs were significantly increased in HCC tissue [29,32], which is consistent with our results.…”

Section: Altered Lipid Species Associated With Hccsupporting

confidence: 93%

Plasma Lipidomic Analysis to Identify Novel Biomarkers for Hepatocellular Carcinoma

Yang

Bai²,

Han

et al. 2017

J. Anal. Test.

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Hepatocellular carcinoma (HCC) accounts for the major primary liver cancer, and its morbidity and mortality rates are very high. Identification of novel biomarkers for the early diagnosis and treatment of this disease is of crucial importance. In this study, a continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF/MS) method was used to detect lipid species in human plasma from HCC patients and healthy controls. As a result, the two groups were clearly separated by principal component analysis. Besides, 23 lipid species with corrected p value \0.05 and fold change [1.5 were proposed as potential lipid biomarkers for HCC. Among them, 9 lipid species, including galactosylceramide (36:5), free fatty acid (20:4), phosphatidylethanolamine (40:6), phosphatidylethanolamine (38:6), diacylglycerol (40:5), diacylglycerol (44:2), lactosylceramide (40:3), phosphatidylcholine (40:6), and free fatty acid (22:5), exhibited excellent ability to distinguish HCC patients from healthy controls with the area under the receiver-operating characteristic curve [0.900, showing promising clinical value. Taken together, these results indicate the great potential of NP/RP 2D LC-QToF/MS method in disease diagnosis, which might be helpful in clinical practice.

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Section: Altered Lipid Species Associated With Hccsupporting

confidence: 93%

Plasma Lipidomic Analysis to Identify Novel Biomarkers for Hepatocellular Carcinoma

Yang

Bai²,

Han

et al. 2017

J. Anal. Test.

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“…Because tumors can recur, however, PDT is combined with other anticancer drugs to improve its therapeutic benefit. Sphingolipids include membrane-bound bioactive lipids that can act as anticancer agents [2]. We and others have shown that stresses, including Pc4-mediated PDT, can perturb the de novo sphingolipid biosynthesis (DNS) pathway, leading to changes in the levels of its intermediates, which are potent regulators of cell death [3] [4].…”

Section: Introductionmentioning

confidence: 99%

Enhanced apoptotic cancer cell killing after Foscan photodynamic therapy combined with fenretinide via de novo sphingolipid biosynthesis pathway

Boppana

DeLor

Buren

et al. 2016

Journal of Photochemistry and Photobiology B: Biology

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We and others have shown that stresses, including photodynamic therapy (PDT)1, can disrupt the de novo sphingolipid biosynthesis pathway, leading to changes in the levels of sphingolipids, and subsequently, modulation of cell death. The de novo sphingolipid biosynthesis pathway includes a ceramide synthase-dependent reaction, giving rise to dihydroceramide, which is then converted in a desaturase-dependent reaction to ceramide. In this study we tested the hypothesis that combining Foscan-mediated PDT with desaturase inhibitor fenretinide (HPR) enhances cancer cell killing. We discovered that by subjecting SCC19 cells, a human head and neck squamous cell carcinoma cell line, to PDT+HPR resulted in enhanced accumulation of C16-dihydroceramide, not ceramide. Concomitantly, mitochondrial depolarization was enhanced by the combined treatment. Enhanced activation of caspase-3 after PDT +HPR was inhibited by FB. Enhanced clonogenic cell death after the combination was sensitive to FB, as well as Bcl2- and caspase inhibitors. Treatment of mouse SCCVII squamous cell carcinoma tumors with PDT+HPR resulted in improved long-term tumor cures. Overall, our data showed that combining PDT with HPR enhanced apoptotic cancer cell killing and antitumor efficacy of PDT. The data suggest the involvement of the de novo sphingolipid biosynthesis pathway in enhanced apoptotic cell killing after PDT+HPR, identify PDT+HPR as a more effective combination than either treatment alone, and that the combination has potential for cancer treatment.

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“…Pyrimidine metabolism, and in general nucleotide metabolism, is widely known to play an important role in cancerous proliferation, as a sufficient pool of nucleotides is necessary for the requisite DNA replication of mitosis during proliferation 38 . Changes were also identified in lipid metabolism pathways; lipid metabolism is known to be implicated in cancer, and lipid signaling mediates many cellular mechanisms, including apoptosis 39 . Changes in lipid pathways could be indicative of some direct effect of menaquinone, an indirect effect mediated by phosphoethanolamine, or an even more indirect effect as the result of induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia

et al. 2015

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Altered metabolism is increasingly acknowledged as an important aspect of cancer, and thus serves as a potentially fertile area for the identification of therapeutic targets or leads. Our recent work using transcriptional data to predict metabolite levels in cancer cells led to preliminary evidence of the antiproliferative role of menaquinone (Vitamin K2) in the Jurkat cell line model of acute lymphoblastic leukemia. However, nothing is known about the direct metabolic impacts of menaquinone in cancer, which could provide insights into its mechanism of action. Here, we used metabolomics to investigate the process by which menaquinone exerts antiproliferative activity on Jurkat cells. We first validated the dose-dependent, semi-selective, pro-apoptotic activity of menaquinone treatment on Jurkat cells relative to non-cancerous lymphoblasts. We then used mass spectrometry-based metabolomics to identify systems-scale changes in metabolic dynamics that are distinct from changes induced in non-cancerous cells or by other chemotherapeutics. One of the most significantly affected metabolites was phosphoethanolamine, which exhibited a two-fold increase in menaquinone-treated Jurkat cells compared to vehicle-treated cells at 24 h, growing to a five-fold increase at 72 h. Phosphoethanolamine elevation was observed prior to the induction of apoptosis, and was not observed in menaquinone-treated lymphoblasts or chemotherapeutic-treated Jurkat cells. We also validated the link between menaquinone and phosphoethanolamine in an ovarian cancer cell line, suggesting potentially broad applicability of their relationship. This metabolomics-based work is the first detailed characterization of the metabolic impacts of menaquinone treatment and the first identified link between phosphoethanolamine and menaquinone-induced apoptosis.

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Lipid Metabolism, Apoptosis and Cancer Therapy

Cited by 354 publications

References 174 publications

Plasma Lipidomic Analysis to Identify Novel Biomarkers for Hepatocellular Carcinoma

Plasma Lipidomic Analysis to Identify Novel Biomarkers for Hepatocellular Carcinoma

Enhanced apoptotic cancer cell killing after Foscan photodynamic therapy combined with fenretinide via de novo sphingolipid biosynthesis pathway

Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia

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