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
Colorectal cancer (CRC) is one of the most common and mortal types of cancer. There is increasing evidence that some polyunsaturated fatty acids (PUFAs) exercise specific inhibitory actions on cancer cells through different mechanisms, as a previous study on CRC cells demonstrated for two very long-...
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| Veröffentlicht in: | Nutrients 2019-12, Vol.11 (12), p.2984 |
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| creator | González-Fernández, María José Fabrikov, Dmitri Ramos-Bueno, Rebeca P Guil-Guerrero, José Luis Ortea, Ignacio |
| description | Colorectal cancer (CRC) is one of the most common and mortal types of cancer. There is increasing evidence that some polyunsaturated fatty acids (PUFAs) exercise specific inhibitory actions on cancer cells through different mechanisms, as a previous study on CRC cells demonstrated for two very long-chain PUFA. These were docosahexaenoic acid (DHA, 22:6
3) and arachidonic acid (ARA, 20:4
6) in the free fatty acid (FFA) form. In this work, similar design and technology have been used to investigate the actions of both DHA and ARA as monoacylglycerol (MAG) molecules, and results have been compared with those obtained using the corresponding FFA. Cell assays revealed that ARA- and DHA-MAG exercised dose- and time-dependent antiproliferative actions, with DHA-MAG acting on cancer cells more efficiently than ARA-MAG. Sequential window acquisition of all theoretical mass spectra (SWATH) - mass spectrometry massive quantitative proteomics, validated by parallel reaction monitoring and followed by pathway analysis, revealed that DHA-MAG had a massive effect in the proteasome complex, while the ARA-MAG main effect was related to DNA replication. Prostaglandin synthesis also resulted as inhibited by DHA-MAG. Results clearly demonstrated the ability of both ARA- and DHA-MAG to induce cell death in colon cancer cells, which suggests a direct relationship between chemical structure and antitumoral actions. |
| doi_str_mv | 10.3390/nu11122984 |
| format | Article |
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3) and arachidonic acid (ARA, 20:4
6) in the free fatty acid (FFA) form. In this work, similar design and technology have been used to investigate the actions of both DHA and ARA as monoacylglycerol (MAG) molecules, and results have been compared with those obtained using the corresponding FFA. Cell assays revealed that ARA- and DHA-MAG exercised dose- and time-dependent antiproliferative actions, with DHA-MAG acting on cancer cells more efficiently than ARA-MAG. Sequential window acquisition of all theoretical mass spectra (SWATH) - mass spectrometry massive quantitative proteomics, validated by parallel reaction monitoring and followed by pathway analysis, revealed that DHA-MAG had a massive effect in the proteasome complex, while the ARA-MAG main effect was related to DNA replication. Prostaglandin synthesis also resulted as inhibited by DHA-MAG. Results clearly demonstrated the ability of both ARA- and DHA-MAG to induce cell death in colon cancer cells, which suggests a direct relationship between chemical structure and antitumoral actions.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu11122984</identifier><identifier>PMID: 31817645</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antineoplastic Agents - pharmacology ; Antitumor activity ; Apoptosis ; Arachidonic acid ; Arachidonic Acid - pharmacology ; Cell Death - drug effects ; Cell growth ; Chromatography ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; DNA Replication - drug effects ; Docosahexaenoic acid ; Docosahexaenoic Acids - pharmacology ; Drug Screening Assays, Antitumor ; Enzymes ; Fatty acids ; Glycerol ; HT29 Cells ; Humans ; Lipids ; Mass Spectrometry ; Monoglycerides - pharmacology ; Proteasome Endopeptidase Complex - drug effects ; Proteins ; Proteomics ; Scientific imaging</subject><ispartof>Nutrients, 2019-12, Vol.11 (12), p.2984</ispartof><rights>2019. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-f2a8b599c9934c67f777b9bebbb98846225f34194fe70356662ed8a15192a3a43</citedby><cites>FETCH-LOGICAL-c406t-f2a8b599c9934c67f777b9bebbb98846225f34194fe70356662ed8a15192a3a43</cites><orcidid>0000-0001-8917-5525 ; 0000-0003-2666-1774</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950369/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950369/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31817645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>González-Fernández, María José</creatorcontrib><creatorcontrib>Fabrikov, Dmitri</creatorcontrib><creatorcontrib>Ramos-Bueno, Rebeca P</creatorcontrib><creatorcontrib>Guil-Guerrero, José Luis</creatorcontrib><creatorcontrib>Ortea, Ignacio</creatorcontrib><title>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</title><title>Nutrients</title><addtitle>Nutrients</addtitle><description>Colorectal cancer (CRC) is one of the most common and mortal types of cancer. There is increasing evidence that some polyunsaturated fatty acids (PUFAs) exercise specific inhibitory actions on cancer cells through different mechanisms, as a previous study on CRC cells demonstrated for two very long-chain PUFA. These were docosahexaenoic acid (DHA, 22:6
3) and arachidonic acid (ARA, 20:4
6) in the free fatty acid (FFA) form. In this work, similar design and technology have been used to investigate the actions of both DHA and ARA as monoacylglycerol (MAG) molecules, and results have been compared with those obtained using the corresponding FFA. Cell assays revealed that ARA- and DHA-MAG exercised dose- and time-dependent antiproliferative actions, with DHA-MAG acting on cancer cells more efficiently than ARA-MAG. Sequential window acquisition of all theoretical mass spectra (SWATH) - mass spectrometry massive quantitative proteomics, validated by parallel reaction monitoring and followed by pathway analysis, revealed that DHA-MAG had a massive effect in the proteasome complex, while the ARA-MAG main effect was related to DNA replication. Prostaglandin synthesis also resulted as inhibited by DHA-MAG. 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There is increasing evidence that some polyunsaturated fatty acids (PUFAs) exercise specific inhibitory actions on cancer cells through different mechanisms, as a previous study on CRC cells demonstrated for two very long-chain PUFA. These were docosahexaenoic acid (DHA, 22:6
3) and arachidonic acid (ARA, 20:4
6) in the free fatty acid (FFA) form. In this work, similar design and technology have been used to investigate the actions of both DHA and ARA as monoacylglycerol (MAG) molecules, and results have been compared with those obtained using the corresponding FFA. Cell assays revealed that ARA- and DHA-MAG exercised dose- and time-dependent antiproliferative actions, with DHA-MAG acting on cancer cells more efficiently than ARA-MAG. Sequential window acquisition of all theoretical mass spectra (SWATH) - mass spectrometry massive quantitative proteomics, validated by parallel reaction monitoring and followed by pathway analysis, revealed that DHA-MAG had a massive effect in the proteasome complex, while the ARA-MAG main effect was related to DNA replication. Prostaglandin synthesis also resulted as inhibited by DHA-MAG. Results clearly demonstrated the ability of both ARA- and DHA-MAG to induce cell death in colon cancer cells, which suggests a direct relationship between chemical structure and antitumoral actions.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31817645</pmid><doi>10.3390/nu11122984</doi><orcidid>https://orcid.org/0000-0001-8917-5525</orcidid><orcidid>https://orcid.org/0000-0003-2666-1774</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Antineoplastic Agents - pharmacology Antitumor activity Apoptosis Arachidonic acid Arachidonic Acid - pharmacology Cell Death - drug effects Cell growth Chromatography Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology DNA Replication - drug effects Docosahexaenoic acid Docosahexaenoic Acids - pharmacology Drug Screening Assays, Antitumor Enzymes Fatty acids Glycerol HT29 Cells Humans Lipids Mass Spectrometry Monoglycerides - pharmacology Proteasome Endopeptidase Complex - drug effects Proteins Proteomics Scientific imaging |
| title | 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 |
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