Anti-cancer Effects of MW-03, a Novel Indole Compound, by Inducing 15-Hydroxyprostaglandin Dehydrogenase and Cellular Growth Inhibition in the LS174T Human Colon Cancer Cell Line
Increases in the expression of prostaglandin E2 (PGE2) are widely known to be involved in aberrant growth in the early stage of colon cancer development. We herein demonstrated that the novel indole compound MW-03 reduced PGE2-induced cAMP formation by catalization to an inactive metabolite by induc...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2017/10/01, Vol.40(10), pp.1806-1812 |
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| creator | Seira, Naofumi Yanagisawa, Naoki Suganami, Akiko Honda, Takuya Wasai, Makiko Regan, John W. Fukushima, Keijo Yamaguchi, Naoto Tamura, Yutaka Arai, Takayoshi Murayama, Toshihiko Fujino, Hiromichi |
| description | Increases in the expression of prostaglandin E2 (PGE2) are widely known to be involved in aberrant growth in the early stage of colon cancer development. We herein demonstrated that the novel indole compound MW-03 reduced PGE2-induced cAMP formation by catalization to an inactive metabolite by inducing 15-hydroxyprostaglandin dehydrogenase through the activation of peroxisome proliferator-activated receptor-γ. MW-03 also inhibited colon cancer cell growth by arresting the cell cycle at the S phase. Although the target of MW-03 for cell cycle inhibition has not yet been identified, these dual anti-cancer effects of MW-03 itself and/or its leading compound(s) on colon cancer cells may reduce colon cancer development and, thus, have potential as a novel treatment for the early stage of this disease. |
| doi_str_mv | 10.1248/bpb.b17-00458 |
| format | Article |
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We herein demonstrated that the novel indole compound MW-03 reduced PGE2-induced cAMP formation by catalization to an inactive metabolite by inducing 15-hydroxyprostaglandin dehydrogenase through the activation of peroxisome proliferator-activated receptor-γ. MW-03 also inhibited colon cancer cell growth by arresting the cell cycle at the S phase. Although the target of MW-03 for cell cycle inhibition has not yet been identified, these dual anti-cancer effects of MW-03 itself and/or its leading compound(s) on colon cancer cells may reduce colon cancer development and, thus, have potential as a novel treatment for the early stage of this disease.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b17-00458</identifier><identifier>PMID: 28966256</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>15-hydroxyprostaglandin dehydrogenase ; 15-Hydroxyprostaglandin dehydrogenase (NAD+) ; Antineoplastic Agents - pharmacology ; Cell cycle ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Colon cancer ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - metabolism ; Colorectal cancer ; Cyclic AMP - metabolism ; Dehydrogenase ; Dehydrogenases ; Dinoprostone - pharmacology ; Humans ; Hydroxyprostaglandin Dehydrogenases - metabolism ; indole compound ; Indoles ; Indoles - pharmacology ; Inhibition ; MW-03 ; peroxisome proliferator-activated receptor-γ ; PPAR gamma - metabolism ; Prostaglandin E2 ; S phase</subject><ispartof>Biological and Pharmaceutical Bulletin, 2017/10/01, Vol.40(10), pp.1806-1812</ispartof><rights>2017 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c703t-a37c99fb490cf89115ccf422f26c1f7793d1ff6f42725da71229fc00fad6e3cc3</citedby><cites>FETCH-LOGICAL-c703t-a37c99fb490cf89115ccf422f26c1f7793d1ff6f42725da71229fc00fad6e3cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28966256$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Seira, Naofumi</creatorcontrib><creatorcontrib>Yanagisawa, Naoki</creatorcontrib><creatorcontrib>Suganami, Akiko</creatorcontrib><creatorcontrib>Honda, Takuya</creatorcontrib><creatorcontrib>Wasai, Makiko</creatorcontrib><creatorcontrib>Regan, John W.</creatorcontrib><creatorcontrib>Fukushima, Keijo</creatorcontrib><creatorcontrib>Yamaguchi, Naoto</creatorcontrib><creatorcontrib>Tamura, Yutaka</creatorcontrib><creatorcontrib>Arai, Takayoshi</creatorcontrib><creatorcontrib>Murayama, Toshihiko</creatorcontrib><creatorcontrib>Fujino, Hiromichi</creatorcontrib><creatorcontrib>Tokushima University</creatorcontrib><creatorcontrib>bDepartment of Bioinformatics</creatorcontrib><creatorcontrib>Graduate School of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>fDepartment of Molecular Pharmacology</creatorcontrib><creatorcontrib>Chiba University</creatorcontrib><creatorcontrib>eDepartment of Pharmacology and Toxicology</creatorcontrib><creatorcontrib>Graduate School of Pharmaceutical Sciences & Graduate School of Bioimedical Sciences</creatorcontrib><creatorcontrib>dDepartment of Chemistry</creatorcontrib><creatorcontrib>The University Arizona</creatorcontrib><creatorcontrib>cDepartment of Molecular Cell Biology</creatorcontrib><creatorcontrib>Graduate School of Science</creatorcontrib><creatorcontrib>Graduate School of Medicine</creatorcontrib><creatorcontrib>aLaboratory of Chemical Pharmacology</creatorcontrib><creatorcontrib>College of Pharmaacy</creatorcontrib><title>Anti-cancer Effects of MW-03, a Novel Indole Compound, by Inducing 15-Hydroxyprostaglandin Dehydrogenase and Cellular Growth Inhibition in the LS174T Human Colon Cancer Cell Line</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Increases in the expression of prostaglandin E2 (PGE2) are widely known to be involved in aberrant growth in the early stage of colon cancer development. We herein demonstrated that the novel indole compound MW-03 reduced PGE2-induced cAMP formation by catalization to an inactive metabolite by inducing 15-hydroxyprostaglandin dehydrogenase through the activation of peroxisome proliferator-activated receptor-γ. MW-03 also inhibited colon cancer cell growth by arresting the cell cycle at the S phase. Although the target of MW-03 for cell cycle inhibition has not yet been identified, these dual anti-cancer effects of MW-03 itself and/or its leading compound(s) on colon cancer cells may reduce colon cancer development and, thus, have potential as a novel treatment for the early stage of this disease.</description><subject>15-hydroxyprostaglandin dehydrogenase</subject><subject>15-Hydroxyprostaglandin dehydrogenase (NAD+)</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colorectal cancer</subject><subject>Cyclic AMP - metabolism</subject><subject>Dehydrogenase</subject><subject>Dehydrogenases</subject><subject>Dinoprostone - pharmacology</subject><subject>Humans</subject><subject>Hydroxyprostaglandin Dehydrogenases - metabolism</subject><subject>indole compound</subject><subject>Indoles</subject><subject>Indoles - pharmacology</subject><subject>Inhibition</subject><subject>MW-03</subject><subject>peroxisome proliferator-activated receptor-γ</subject><subject>PPAR gamma - metabolism</subject><subject>Prostaglandin E2</subject><subject>S phase</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU9v1DAQxSMEoqVw5IosceHQFP-J4_hYbctupQUOFHG0HMfe9SprL3YC7NfiEzJpyiJxsaWZn988zyuK1wRfEVo179tDe9USUWJc8eZJcU5YJUpOCX9anGNJmrImvDkrXuS8wxgLTNnz4ow2sq4pr8-L39dh8KXRwdiEbp2zZsgoOvTxW4nZJdLoU_xhe3QXuthbtIj7QxxDd4na41QbjQ8bRHi5OnYp_joeUsyD3vQ6dD6gG7udyhsbdLYIamhh-37sdULLFH8OW5DY-tYPPgYE_LC1aP2FiOoerca9DjCuh85iNje9RWsf7MvimdN9tq8e74vi64fb-8WqXH9e3i2u16URmA2lZsJI6dpKYuMaSQg3xlWUOlob4oSQrCPO1VASlHdaEEqlMxg73dWWGcMuinezLvzq-2jzoPY-G3Chg41jVkRWXBApWQPo2__QXRxTAHcTJRhndVUBVc6UgTXlZJ06JL_X6agIVlOYCsJUEKZ6CBP4N4-qY7u33Yn-mx4AyxmArjcaltXDfv7NNlm0HnaoKJ5FMQzCVCrS4BoOQhmhkhMGSjez0m7Kz55G6TR409sHYxWefMJ5cnhqm61Oygb2B8kiyL4</recordid><startdate>2017</startdate><enddate>2017</enddate><creator>Seira, Naofumi</creator><creator>Yanagisawa, Naoki</creator><creator>Suganami, Akiko</creator><creator>Honda, Takuya</creator><creator>Wasai, Makiko</creator><creator>Regan, John W.</creator><creator>Fukushima, Keijo</creator><creator>Yamaguchi, Naoto</creator><creator>Tamura, Yutaka</creator><creator>Arai, Takayoshi</creator><creator>Murayama, Toshihiko</creator><creator>Fujino, Hiromichi</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>2017</creationdate><title>Anti-cancer Effects of MW-03, a Novel Indole Compound, by Inducing 15-Hydroxyprostaglandin Dehydrogenase and Cellular Growth Inhibition in the LS174T Human Colon Cancer Cell Line</title><author>Seira, Naofumi ; Yanagisawa, Naoki ; Suganami, Akiko ; Honda, Takuya ; Wasai, Makiko ; Regan, John W. ; Fukushima, Keijo ; Yamaguchi, Naoto ; Tamura, Yutaka ; Arai, Takayoshi ; Murayama, Toshihiko ; Fujino, Hiromichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c703t-a37c99fb490cf89115ccf422f26c1f7793d1ff6f42725da71229fc00fad6e3cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>15-hydroxyprostaglandin dehydrogenase</topic><topic>15-Hydroxyprostaglandin dehydrogenase (NAD+)</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colorectal cancer</topic><topic>Cyclic AMP - metabolism</topic><topic>Dehydrogenase</topic><topic>Dehydrogenases</topic><topic>Dinoprostone - pharmacology</topic><topic>Humans</topic><topic>Hydroxyprostaglandin Dehydrogenases - metabolism</topic><topic>indole compound</topic><topic>Indoles</topic><topic>Indoles - pharmacology</topic><topic>Inhibition</topic><topic>MW-03</topic><topic>peroxisome proliferator-activated receptor-γ</topic><topic>PPAR gamma - metabolism</topic><topic>Prostaglandin E2</topic><topic>S phase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seira, Naofumi</creatorcontrib><creatorcontrib>Yanagisawa, Naoki</creatorcontrib><creatorcontrib>Suganami, Akiko</creatorcontrib><creatorcontrib>Honda, Takuya</creatorcontrib><creatorcontrib>Wasai, Makiko</creatorcontrib><creatorcontrib>Regan, John W.</creatorcontrib><creatorcontrib>Fukushima, Keijo</creatorcontrib><creatorcontrib>Yamaguchi, Naoto</creatorcontrib><creatorcontrib>Tamura, Yutaka</creatorcontrib><creatorcontrib>Arai, Takayoshi</creatorcontrib><creatorcontrib>Murayama, Toshihiko</creatorcontrib><creatorcontrib>Fujino, Hiromichi</creatorcontrib><creatorcontrib>Tokushima University</creatorcontrib><creatorcontrib>bDepartment of Bioinformatics</creatorcontrib><creatorcontrib>Graduate School of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>fDepartment of Molecular Pharmacology</creatorcontrib><creatorcontrib>Chiba University</creatorcontrib><creatorcontrib>eDepartment of Pharmacology and Toxicology</creatorcontrib><creatorcontrib>Graduate School of Pharmaceutical Sciences & Graduate School of Bioimedical Sciences</creatorcontrib><creatorcontrib>dDepartment of Chemistry</creatorcontrib><creatorcontrib>The University Arizona</creatorcontrib><creatorcontrib>cDepartment of Molecular Cell Biology</creatorcontrib><creatorcontrib>Graduate School of Science</creatorcontrib><creatorcontrib>Graduate School of Medicine</creatorcontrib><creatorcontrib>aLaboratory of Chemical Pharmacology</creatorcontrib><creatorcontrib>College of Pharmaacy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - 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| subjects | 15-hydroxyprostaglandin dehydrogenase 15-Hydroxyprostaglandin dehydrogenase (NAD+) Antineoplastic Agents - pharmacology Cell cycle Cell Line, Tumor Cell Proliferation - drug effects Colon cancer Colonic Neoplasms - drug therapy Colonic Neoplasms - metabolism Colorectal cancer Cyclic AMP - metabolism Dehydrogenase Dehydrogenases Dinoprostone - pharmacology Humans Hydroxyprostaglandin Dehydrogenases - metabolism indole compound Indoles Indoles - pharmacology Inhibition MW-03 peroxisome proliferator-activated receptor-γ PPAR gamma - metabolism Prostaglandin E2 S phase |
| title | Anti-cancer Effects of MW-03, a Novel Indole Compound, by Inducing 15-Hydroxyprostaglandin Dehydrogenase and Cellular Growth Inhibition in the LS174T Human Colon Cancer Cell Line |
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