Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells

The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in me...

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Veröffentlicht in:PloS one 2016-03, Vol.11 (3), p.e0151179
Hauptverfasser: Smith, Tim A D, Phyu, Su M
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description The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U)]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK), CTP:phosphocholine cytidylyl transferase (CCT) and PtdCho-phospholipase C (PLC) were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography. Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U)]glucose. This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.
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Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U)]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK), CTP:phosphocholine cytidylyl transferase (CCT) and PtdCho-phospholipase C (PLC) were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography. Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U)]glucose. This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0151179</identifier><identifier>PMID: 26959405</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Analysis ; Antidiabetics ; Biology and Life Sciences ; Breast cancer ; Breast Neoplasms - metabolism ; Cancer ; Care and treatment ; Cell growth ; Cell Line, Tumor ; Cellular signal transduction ; Choline ; Choline - metabolism ; Choline kinase ; Chromatography ; CTP:phosphocholine cytidylyltransferase ; Diabetes mellitus ; Fatty acids ; Female ; Glucose ; Glucose metabolism ; Glycerol ; Humans ; Influence ; Intracellular signalling ; Kinases ; Lecithin ; Lipase ; Lipid metabolism ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Metformin ; Metformin - pharmacology ; Phosphatidylcholine ; Phosphatidylcholines - metabolism ; Phospholipase ; Phospholipase C ; Phospholipids ; Phospholipids - metabolism ; Physical Sciences ; Physiological aspects ; Research and analysis methods ; Rodents ; Synthesis ; Thin layer chromatography ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2016-03, Vol.11 (3), p.e0151179</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Smith, Phyu. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U)]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK), CTP:phosphocholine cytidylyl transferase (CCT) and PtdCho-phospholipase C (PLC) were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography. Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U)]glucose. This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.</description><subject>Accumulation</subject><subject>Analysis</subject><subject>Antidiabetics</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cellular signal transduction</subject><subject>Choline</subject><subject>Choline - metabolism</subject><subject>Choline kinase</subject><subject>Chromatography</subject><subject>CTP:phosphocholine cytidylyltransferase</subject><subject>Diabetes mellitus</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Glycerol</subject><subject>Humans</subject><subject>Influence</subject><subject>Intracellular signalling</subject><subject>Kinases</subject><subject>Lecithin</subject><subject>Lipase</subject><subject>Lipid metabolism</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metformin</subject><subject>Metformin - pharmacology</subject><subject>Phosphatidylcholine</subject><subject>Phosphatidylcholines - metabolism</subject><subject>Phospholipase</subject><subject>Phospholipase C</subject><subject>Phospholipids</subject><subject>Phospholipids - metabolism</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Research and analysis methods</subject><subject>Rodents</subject><subject>Synthesis</subject><subject>Thin layer chromatography</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLgujFjPlsmxthd_waWFnRxduQpqfTDGnTTVrRf29mprtMZS-khJykz3lPz-mbJM8xWmKa43dbN_pO2WXvOlgizDHOxYPkFAtKFhlB9OFRfJI8CWGLEKdFlj1OTkgmuGCInyYXX2GonW9Nl34A7cbeQki_NS70jbOmN1UaAVXGOLRphC48qDCkK9Vp8OkKrA1Pk0e1sgGeTftZcv3p4_Xqy-Ly6vN6dX650Jkgw4JjUYgMUcqqCgCKHKgWRBV1KXgFrBK1QBWpiizuFKGCgMYUlzweS1UTepa8PMj21gU5dR8kznMWF8pYJNYHonJqK3tvWuX_SKeM3F84v5HKD0ZbkIhhTpkGyIViGWaqrjUhiiASJ5TzXbX3U7WxbKHS0A1e2Zno_E1nGrlxvyTLCyYoigJvJgHvbkYIg2xN0HFeqgM37r-bFDQnlEf01T_o_d1N1EbFBkxXu1hX70TlOeNRBtN92eU9VHwqaI2OVqlNvJ8lvJ0lRGaA38NGjSHI9Y_v_89e_Zyzr4_YBpQdmuDsOBjXhTnIDqD2LgQP9d2QMZI7p99OQ-6cLienx7QXxz_oLunW2vQvYzf2rA</recordid><startdate>20160309</startdate><enddate>20160309</enddate><creator>Smith, Tim A D</creator><creator>Phyu, Su M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160309</creationdate><title>Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells</title><author>Smith, Tim A D ; Phyu, Su M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5198960334ddeee87e3c92a8fb95de4d9f90d2d86f9030082ec131b5f90baf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Accumulation</topic><topic>Analysis</topic><topic>Antidiabetics</topic><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cellular signal transduction</topic><topic>Choline</topic><topic>Choline - metabolism</topic><topic>Choline kinase</topic><topic>Chromatography</topic><topic>CTP:phosphocholine cytidylyltransferase</topic><topic>Diabetes mellitus</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>Glycerol</topic><topic>Humans</topic><topic>Influence</topic><topic>Intracellular signalling</topic><topic>Kinases</topic><topic>Lecithin</topic><topic>Lipase</topic><topic>Lipid metabolism</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metformin</topic><topic>Metformin - pharmacology</topic><topic>Phosphatidylcholine</topic><topic>Phosphatidylcholines - metabolism</topic><topic>Phospholipase</topic><topic>Phospholipase C</topic><topic>Phospholipids</topic><topic>Phospholipids - metabolism</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Research and analysis methods</topic><topic>Rodents</topic><topic>Synthesis</topic><topic>Thin layer chromatography</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, Tim A D</creatorcontrib><creatorcontrib>Phyu, Su M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; 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Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U)]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK), CTP:phosphocholine cytidylyl transferase (CCT) and PtdCho-phospholipase C (PLC) were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography. Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U)]glucose. This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26959405</pmid><doi>10.1371/journal.pone.0151179</doi><oa>free_for_read</oa></addata></record>
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subjects Accumulation
Analysis
Antidiabetics
Biology and Life Sciences
Breast cancer
Breast Neoplasms - metabolism
Cancer
Care and treatment
Cell growth
Cell Line, Tumor
Cellular signal transduction
Choline
Choline - metabolism
Choline kinase
Chromatography
CTP:phosphocholine cytidylyltransferase
Diabetes mellitus
Fatty acids
Female
Glucose
Glucose metabolism
Glycerol
Humans
Influence
Intracellular signalling
Kinases
Lecithin
Lipase
Lipid metabolism
Medicine and Health Sciences
Metabolism
Metabolites
Metformin
Metformin - pharmacology
Phosphatidylcholine
Phosphatidylcholines - metabolism
Phospholipase
Phospholipase C
Phospholipids
Phospholipids - metabolism
Physical Sciences
Physiological aspects
Research and analysis methods
Rodents
Synthesis
Thin layer chromatography
Tumor cell lines
Tumors
title Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells
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