Umbelliprenin Increases the M1/M2 Ratio of Macrophage Polarization and Improves the M1 Macrophage Activity in THP-1 Cells Cocultured with AGS Cells
Background. Gastric adenocarcinoma is the fifth most diagnosed malignancy in the world. The immune system consists of a heterogeneous mixture of macrophages that defense the body through phagocytosis and the production of different cytokines and chemokines. Tumors cause macrophages to polarize diffe...
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description | Background. Gastric adenocarcinoma is the fifth most diagnosed malignancy in the world. The immune system consists of a heterogeneous mixture of macrophages that defense the body through phagocytosis and the production of different cytokines and chemokines. Tumors cause macrophages to polarize differently in the manner of their favorite growth and angiogenesis. Umbelliprenin, a natural sesquiterpene coumarin, has been shown to have anticancer properties against some tumors, including gastric adenocarcinoma. The aim of our study was to investigate the effect of umbelliprenin on the polarization of macrophages in addition to the measurement of some of the soluble factors they produce. Method. The values of IC5 and IC50 for umbelliprenin in the AGS and THP-1 cells were estimated using the MTT assay. THP-1 cells were treated with 10 μM umbelliprenin, either alone or cocultured with AGS cells. Flow cytometry analysis of treated THP-1 cells was performed for CD68, CD86, and CD206 markers to evaluate M0, M1, and M2 macrophages polarization, respectively. AGS cells were assessed for apoptosis and necrosis by flow cytometry after labeling with Annexin V-FITC and propidium iodide. Interleukin- (IL-) 10 and IL-12 contents were measured in the supernatant by the ELISA method. Griess Reaction assay technique was used to determine nitric oxide (NO) concentration. Results. The results of the MTT showed lower toxicity of umbelliprenin in THP-1 (IC50 = 75.79) compared to the AGS cell line (IC50 = 48.81). Umbelliprenin significantly increased the M1/M2 ratio. IL-10 content decreased significantly in the supernatant of M1 and M2 cells after umbelliprenin treatment, while IL-12 increased in the supernatant of M1 cells and decreased in the supernatant of the M2 cells. Umbelliprenin caused an increase in the NO in the supernatant of the M1 cells. Conclusion. Umbelliprenin alters the macrophage’s secretions and its phenotypes in favor of tumor suppression. |
doi_str_mv | 10.1155/2021/9927747 |
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Gastric adenocarcinoma is the fifth most diagnosed malignancy in the world. The immune system consists of a heterogeneous mixture of macrophages that defense the body through phagocytosis and the production of different cytokines and chemokines. Tumors cause macrophages to polarize differently in the manner of their favorite growth and angiogenesis. Umbelliprenin, a natural sesquiterpene coumarin, has been shown to have anticancer properties against some tumors, including gastric adenocarcinoma. The aim of our study was to investigate the effect of umbelliprenin on the polarization of macrophages in addition to the measurement of some of the soluble factors they produce. Method. The values of IC5 and IC50 for umbelliprenin in the AGS and THP-1 cells were estimated using the MTT assay. THP-1 cells were treated with 10 μM umbelliprenin, either alone or cocultured with AGS cells. Flow cytometry analysis of treated THP-1 cells was performed for CD68, CD86, and CD206 markers to evaluate M0, M1, and M2 macrophages polarization, respectively. AGS cells were assessed for apoptosis and necrosis by flow cytometry after labeling with Annexin V-FITC and propidium iodide. Interleukin- (IL-) 10 and IL-12 contents were measured in the supernatant by the ELISA method. Griess Reaction assay technique was used to determine nitric oxide (NO) concentration. Results. The results of the MTT showed lower toxicity of umbelliprenin in THP-1 (IC50 = 75.79) compared to the AGS cell line (IC50 = 48.81). Umbelliprenin significantly increased the M1/M2 ratio. IL-10 content decreased significantly in the supernatant of M1 and M2 cells after umbelliprenin treatment, while IL-12 increased in the supernatant of M1 cells and decreased in the supernatant of the M2 cells. Umbelliprenin caused an increase in the NO in the supernatant of the M1 cells. Conclusion. Umbelliprenin alters the macrophage’s secretions and its phenotypes in favor of tumor suppression.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2021/9927747</identifier><identifier>PMID: 34335844</identifier><language>eng</language><publisher>New York: Hindawi</publisher><subject>Adenocarcinoma ; Angiogenesis ; Annexin V ; Apoptosis ; Cancer ; CD86 antigen ; Cell cycle ; Chemokines ; Coumarin ; Enzyme-linked immunosorbent assay ; Flow cytometry ; Gastric cancer ; Immune system ; Interleukin 10 ; Interleukin 12 ; Macrophages ; Malignancy ; Medical prognosis ; Nitric oxide ; Phagocytosis ; Phenotypes ; Polarization ; Propidium iodide ; Secretions ; Toxicity ; Tumor suppression ; Tumors</subject><ispartof>Evidence-based complementary and alternative medicine, 2021, Vol.2021 (NA), p.1-9</ispartof><rights>Copyright © 2021 MohammadTaher Bahrami et al.</rights><rights>Copyright © 2021 MohammadTaher Bahrami et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 MohammadTaher Bahrami et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-cb5faf19ac7603dabd352ad6cf223db139f4f410903f6f55e8a9159a82805bc83</citedby><cites>FETCH-LOGICAL-c458t-cb5faf19ac7603dabd352ad6cf223db139f4f410903f6f55e8a9159a82805bc83</cites><orcidid>0000-0001-5216-2448 ; 0000-0002-5669-3235 ; 0000-0002-7242-5839 ; 0000-0002-1102-8119</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/PMC8294985/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294985/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids></links><search><contributor>Cai, Yu</contributor><creatorcontrib>Bahrami, MohammadTaher</creatorcontrib><creatorcontrib>Haji Molla Hoseini, Mostafa</creatorcontrib><creatorcontrib>Rezaei, Mitra</creatorcontrib><creatorcontrib>Ziai, Seyed Ali</creatorcontrib><title>Umbelliprenin Increases the M1/M2 Ratio of Macrophage Polarization and Improves the M1 Macrophage Activity in THP-1 Cells Cocultured with AGS Cells</title><title>Evidence-based complementary and alternative medicine</title><description>Background. Gastric adenocarcinoma is the fifth most diagnosed malignancy in the world. The immune system consists of a heterogeneous mixture of macrophages that defense the body through phagocytosis and the production of different cytokines and chemokines. Tumors cause macrophages to polarize differently in the manner of their favorite growth and angiogenesis. Umbelliprenin, a natural sesquiterpene coumarin, has been shown to have anticancer properties against some tumors, including gastric adenocarcinoma. The aim of our study was to investigate the effect of umbelliprenin on the polarization of macrophages in addition to the measurement of some of the soluble factors they produce. Method. The values of IC5 and IC50 for umbelliprenin in the AGS and THP-1 cells were estimated using the MTT assay. THP-1 cells were treated with 10 μM umbelliprenin, either alone or cocultured with AGS cells. Flow cytometry analysis of treated THP-1 cells was performed for CD68, CD86, and CD206 markers to evaluate M0, M1, and M2 macrophages polarization, respectively. AGS cells were assessed for apoptosis and necrosis by flow cytometry after labeling with Annexin V-FITC and propidium iodide. Interleukin- (IL-) 10 and IL-12 contents were measured in the supernatant by the ELISA method. Griess Reaction assay technique was used to determine nitric oxide (NO) concentration. Results. The results of the MTT showed lower toxicity of umbelliprenin in THP-1 (IC50 = 75.79) compared to the AGS cell line (IC50 = 48.81). Umbelliprenin significantly increased the M1/M2 ratio. IL-10 content decreased significantly in the supernatant of M1 and M2 cells after umbelliprenin treatment, while IL-12 increased in the supernatant of M1 cells and decreased in the supernatant of the M2 cells. Umbelliprenin caused an increase in the NO in the supernatant of the M1 cells. Conclusion. Umbelliprenin alters the macrophage’s secretions and its phenotypes in favor of tumor suppression.</description><subject>Adenocarcinoma</subject><subject>Angiogenesis</subject><subject>Annexin V</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>CD86 antigen</subject><subject>Cell cycle</subject><subject>Chemokines</subject><subject>Coumarin</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Flow cytometry</subject><subject>Gastric cancer</subject><subject>Immune system</subject><subject>Interleukin 10</subject><subject>Interleukin 12</subject><subject>Macrophages</subject><subject>Malignancy</subject><subject>Medical prognosis</subject><subject>Nitric oxide</subject><subject>Phagocytosis</subject><subject>Phenotypes</subject><subject>Polarization</subject><subject>Propidium iodide</subject><subject>Secretions</subject><subject>Toxicity</subject><subject>Tumor suppression</subject><subject>Tumors</subject><issn>1741-427X</issn><issn>1741-4288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk9rFDEchgdRbK3e_AABL4KOm7-T5CIsi7YLXSzagreQySSdlJlkm8xsqV_DL-wMuyzqQU8JvE-eJD_eoniN4AeEGFtgiNFCSsw55U-KU8QpKikW4ulxz7-fFC9yvoMQS8758-KEUEKYoPS0-HnT17br_DbZ4ANYB5OszjaDobVggxYbDL7qwUcQHdhok-K21bcWXMVOJ_9jTgLQoQHrfpvi7njud3ZpBr_zwyOY_NcXVyUCq-nGDFbRjN0wJtuABz-0YHn-bZ-8LJ453WX76rCeFTefP12vLsrLL-fr1fKyNJSJoTQ1c9ohqQ2vIGl03RCGdVMZhzFpakSko44iKCFxlWPMCi0Rk1pgAVltBDkrPu6927HubWNsGJLu1Db5XqdHFbVXfybBt-o27pTAkkrBJsHbgyDF-9HmQfU-m-kLOtg4ZoUrVElaUUz_jzLGGRFCztY3f6F3cUxhmsRMUSE4hnCi3u-pac45J-uO70ZQzcVQczHUoRgT_m6Ptz40-sH_m_4F48C2fw</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Bahrami, MohammadTaher</creator><creator>Haji Molla Hoseini, Mostafa</creator><creator>Rezaei, Mitra</creator><creator>Ziai, Seyed Ali</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5216-2448</orcidid><orcidid>https://orcid.org/0000-0002-5669-3235</orcidid><orcidid>https://orcid.org/0000-0002-7242-5839</orcidid><orcidid>https://orcid.org/0000-0002-1102-8119</orcidid></search><sort><creationdate>2021</creationdate><title>Umbelliprenin Increases the M1/M2 Ratio of Macrophage Polarization and Improves the M1 Macrophage Activity in THP-1 Cells Cocultured with AGS Cells</title><author>Bahrami, MohammadTaher ; Haji Molla Hoseini, Mostafa ; Rezaei, Mitra ; Ziai, Seyed Ali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-cb5faf19ac7603dabd352ad6cf223db139f4f410903f6f55e8a9159a82805bc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma</topic><topic>Angiogenesis</topic><topic>Annexin V</topic><topic>Apoptosis</topic><topic>Cancer</topic><topic>CD86 antigen</topic><topic>Cell cycle</topic><topic>Chemokines</topic><topic>Coumarin</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Flow cytometry</topic><topic>Gastric cancer</topic><topic>Immune system</topic><topic>Interleukin 10</topic><topic>Interleukin 12</topic><topic>Macrophages</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Nitric oxide</topic><topic>Phagocytosis</topic><topic>Phenotypes</topic><topic>Polarization</topic><topic>Propidium iodide</topic><topic>Secretions</topic><topic>Toxicity</topic><topic>Tumor suppression</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bahrami, MohammadTaher</creatorcontrib><creatorcontrib>Haji Molla Hoseini, Mostafa</creatorcontrib><creatorcontrib>Rezaei, Mitra</creatorcontrib><creatorcontrib>Ziai, Seyed Ali</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Evidence-based complementary and alternative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bahrami, MohammadTaher</au><au>Haji Molla Hoseini, Mostafa</au><au>Rezaei, Mitra</au><au>Ziai, Seyed Ali</au><au>Cai, Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Umbelliprenin Increases the M1/M2 Ratio of Macrophage Polarization and Improves the M1 Macrophage Activity in THP-1 Cells Cocultured with AGS Cells</atitle><jtitle>Evidence-based complementary and alternative medicine</jtitle><date>2021</date><risdate>2021</risdate><volume>2021</volume><issue>NA</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>Background. Gastric adenocarcinoma is the fifth most diagnosed malignancy in the world. The immune system consists of a heterogeneous mixture of macrophages that defense the body through phagocytosis and the production of different cytokines and chemokines. Tumors cause macrophages to polarize differently in the manner of their favorite growth and angiogenesis. Umbelliprenin, a natural sesquiterpene coumarin, has been shown to have anticancer properties against some tumors, including gastric adenocarcinoma. The aim of our study was to investigate the effect of umbelliprenin on the polarization of macrophages in addition to the measurement of some of the soluble factors they produce. Method. The values of IC5 and IC50 for umbelliprenin in the AGS and THP-1 cells were estimated using the MTT assay. THP-1 cells were treated with 10 μM umbelliprenin, either alone or cocultured with AGS cells. Flow cytometry analysis of treated THP-1 cells was performed for CD68, CD86, and CD206 markers to evaluate M0, M1, and M2 macrophages polarization, respectively. AGS cells were assessed for apoptosis and necrosis by flow cytometry after labeling with Annexin V-FITC and propidium iodide. Interleukin- (IL-) 10 and IL-12 contents were measured in the supernatant by the ELISA method. Griess Reaction assay technique was used to determine nitric oxide (NO) concentration. Results. The results of the MTT showed lower toxicity of umbelliprenin in THP-1 (IC50 = 75.79) compared to the AGS cell line (IC50 = 48.81). Umbelliprenin significantly increased the M1/M2 ratio. IL-10 content decreased significantly in the supernatant of M1 and M2 cells after umbelliprenin treatment, while IL-12 increased in the supernatant of M1 cells and decreased in the supernatant of the M2 cells. Umbelliprenin caused an increase in the NO in the supernatant of the M1 cells. Conclusion. Umbelliprenin alters the macrophage’s secretions and its phenotypes in favor of tumor suppression.</abstract><cop>New York</cop><pub>Hindawi</pub><pmid>34335844</pmid><doi>10.1155/2021/9927747</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-5216-2448</orcidid><orcidid>https://orcid.org/0000-0002-5669-3235</orcidid><orcidid>https://orcid.org/0000-0002-7242-5839</orcidid><orcidid>https://orcid.org/0000-0002-1102-8119</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adenocarcinoma Angiogenesis Annexin V Apoptosis Cancer CD86 antigen Cell cycle Chemokines Coumarin Enzyme-linked immunosorbent assay Flow cytometry Gastric cancer Immune system Interleukin 10 Interleukin 12 Macrophages Malignancy Medical prognosis Nitric oxide Phagocytosis Phenotypes Polarization Propidium iodide Secretions Toxicity Tumor suppression Tumors |
title | Umbelliprenin Increases the M1/M2 Ratio of Macrophage Polarization and Improves the M1 Macrophage Activity in THP-1 Cells Cocultured with AGS Cells |
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