TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells
Human glyoxalase I (hGLO I) is a rate-limiting enzyme in the pathway for detoxification of apoptosis-inducible methylglyoxal (MG), which is the side product of tumor-specific aerobic glycolysis. GLO I has been reported to be overexpressed in various types of cancer cells, and has been expected as an...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2016/05/01, Vol.39(5), pp.869-873 |
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| creator | Takasawa, Ryoko Shimada, Nami Uchiro, Hiromi Takahashi, Satoshi Yoshimori, Atsushi Tanuma, Sei-ichi |
| description | Human glyoxalase I (hGLO I) is a rate-limiting enzyme in the pathway for detoxification of apoptosis-inducible methylglyoxal (MG), which is the side product of tumor-specific aerobic glycolysis. GLO I has been reported to be overexpressed in various types of cancer cells, and has been expected as an attractive target for the development of new anticancer drugs. We previously discovered a novel inhibitor of hGLO I, named TLSC702, by our in silico screening method. Here, we show that TLSC702 inhibits the proliferation of human leukemia HL-60 cells and induces apoptosis in a dose-dependent manner. In addition, TLSC702 more significantly inhibits the proliferation of human lung cancer NCI-H522 cells, which highly express GLO I, than that of GLO I lower-expressing human lung cancer NCI-H460 cells. Furthermore, this antiproliferative effect of TLSC702 on NCI-H522 cells is in a dose- and time-dependent manner. These results suggest that TLSC702 can induce apoptosis in tumor cells by GLO I inhibition, which lead to accumulation of MG. Taken together, TLSC702 could become a unique seed compound for the generation of novel chemotherapeutic drugs targeting GLO I-dependent human tumors. |
| doi_str_mv | 10.1248/bpb.b15-00710 |
| format | Article |
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GLO I has been reported to be overexpressed in various types of cancer cells, and has been expected as an attractive target for the development of new anticancer drugs. We previously discovered a novel inhibitor of hGLO I, named TLSC702, by our in silico screening method. Here, we show that TLSC702 inhibits the proliferation of human leukemia HL-60 cells and induces apoptosis in a dose-dependent manner. In addition, TLSC702 more significantly inhibits the proliferation of human lung cancer NCI-H522 cells, which highly express GLO I, than that of GLO I lower-expressing human lung cancer NCI-H460 cells. Furthermore, this antiproliferative effect of TLSC702 on NCI-H522 cells is in a dose- and time-dependent manner. These results suggest that TLSC702 can induce apoptosis in tumor cells by GLO I inhibition, which lead to accumulation of MG. Taken together, TLSC702 could become a unique seed compound for the generation of novel chemotherapeutic drugs targeting GLO I-dependent human tumors.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b15-00710</identifier><identifier>PMID: 27150153</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>anticancer drug ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Butyrates - pharmacology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; DNA Fragmentation ; glyoxalase I ; Humans ; inhibitor ; Lactoylglutathione Lyase - antagonists & inhibitors ; Thiazoles - pharmacology</subject><ispartof>Biological and Pharmaceutical Bulletin, 2016/05/01, Vol.39(5), pp.869-873</ispartof><rights>2016 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c702t-a178db9a34959a78f84a7540f95c9740e63c2eb0a070edc31480b8047fbc61873</citedby><cites>FETCH-LOGICAL-c702t-a178db9a34959a78f84a7540f95c9740e63c2eb0a070edc31480b8047fbc61873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27150153$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takasawa, Ryoko</creatorcontrib><creatorcontrib>Shimada, Nami</creatorcontrib><creatorcontrib>Uchiro, Hiromi</creatorcontrib><creatorcontrib>Takahashi, Satoshi</creatorcontrib><creatorcontrib>Yoshimori, Atsushi</creatorcontrib><creatorcontrib>Tanuma, Sei-ichi</creatorcontrib><creatorcontrib>Tokyo University of Science</creatorcontrib><creatorcontrib>Inc</creatorcontrib><creatorcontrib>bInstitute for Theoretical Medicine</creatorcontrib><creatorcontrib>aFaculty of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>cGenome & Drug Research Center</creatorcontrib><title>TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Human glyoxalase I (hGLO I) is a rate-limiting enzyme in the pathway for detoxification of apoptosis-inducible methylglyoxal (MG), which is the side product of tumor-specific aerobic glycolysis. GLO I has been reported to be overexpressed in various types of cancer cells, and has been expected as an attractive target for the development of new anticancer drugs. We previously discovered a novel inhibitor of hGLO I, named TLSC702, by our in silico screening method. Here, we show that TLSC702 inhibits the proliferation of human leukemia HL-60 cells and induces apoptosis in a dose-dependent manner. In addition, TLSC702 more significantly inhibits the proliferation of human lung cancer NCI-H522 cells, which highly express GLO I, than that of GLO I lower-expressing human lung cancer NCI-H460 cells. Furthermore, this antiproliferative effect of TLSC702 on NCI-H522 cells is in a dose- and time-dependent manner. These results suggest that TLSC702 can induce apoptosis in tumor cells by GLO I inhibition, which lead to accumulation of MG. Taken together, TLSC702 could become a unique seed compound for the generation of novel chemotherapeutic drugs targeting GLO I-dependent human tumors.</description><subject>anticancer drug</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Butyrates - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>DNA Fragmentation</subject><subject>glyoxalase I</subject><subject>Humans</subject><subject>inhibitor</subject><subject>Lactoylglutathione Lyase - antagonists & inhibitors</subject><subject>Thiazoles - pharmacology</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkEFvEzEQhS0EomnhyBVZ4sKhW8Zre20fqxVNI0UgQThbtuOljrzrsN6t6L_HSUqQuMxIns_vPT2E3hG4ITWTn-ze3ljCKwBB4AVaEMpExWvCX6IFKCKrhnB5gS5z3kFhoKav0UUtCAfC6QJ926y_t-X1Ghv8JT36iFfDQ7BhSiNOHb6fezPgZXxKv0002ePVdQG2s_MZ3-7Tfko5ZBwGvJn78qP1MeY36FVnYvZvn_cV-nH3edPeV-uvy1V7u65c8ZsqQ4TcWmUoU1wZITvJjOAMOsWdEgx8Q13tLZgS2m8dJUyClcBEZ11DpKBX6ONJdz-mX7PPk-5DdiWBGXyasy76ggngkhb0w3_oLs3jUNIdKagl56xQ1YlyY8p59J3ej6E345MmoA9l61K2LmXrY9mFf_-sOtveb8_033YLsDwB5RqciWmIYfD_vF0WNqSYdA2kKaJUQdGulQbZHIagdcMVFQer9qS0y5P56c9WZpyCi_4YjCrND-Mc8Hx1D2bUfqB_AMXipSA</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Takasawa, Ryoko</creator><creator>Shimada, Nami</creator><creator>Uchiro, Hiromi</creator><creator>Takahashi, Satoshi</creator><creator>Yoshimori, Atsushi</creator><creator>Tanuma, Sei-ichi</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>20160501</creationdate><title>TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells</title><author>Takasawa, Ryoko ; Shimada, Nami ; Uchiro, Hiromi ; Takahashi, Satoshi ; Yoshimori, Atsushi ; Tanuma, Sei-ichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c702t-a178db9a34959a78f84a7540f95c9740e63c2eb0a070edc31480b8047fbc61873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>anticancer drug</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Butyrates - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>DNA Fragmentation</topic><topic>glyoxalase I</topic><topic>Humans</topic><topic>inhibitor</topic><topic>Lactoylglutathione Lyase - antagonists & inhibitors</topic><topic>Thiazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takasawa, Ryoko</creatorcontrib><creatorcontrib>Shimada, Nami</creatorcontrib><creatorcontrib>Uchiro, Hiromi</creatorcontrib><creatorcontrib>Takahashi, Satoshi</creatorcontrib><creatorcontrib>Yoshimori, Atsushi</creatorcontrib><creatorcontrib>Tanuma, Sei-ichi</creatorcontrib><creatorcontrib>Tokyo University of Science</creatorcontrib><creatorcontrib>Inc</creatorcontrib><creatorcontrib>bInstitute for Theoretical Medicine</creatorcontrib><creatorcontrib>aFaculty of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>cGenome & Drug Research Center</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 - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takasawa, Ryoko</au><au>Shimada, Nami</au><au>Uchiro, Hiromi</au><au>Takahashi, Satoshi</au><au>Yoshimori, Atsushi</au><au>Tanuma, Sei-ichi</au><aucorp>Tokyo University of Science</aucorp><aucorp>Inc</aucorp><aucorp>bInstitute for Theoretical Medicine</aucorp><aucorp>aFaculty of Pharmaceutical Sciences</aucorp><aucorp>cGenome & Drug Research Center</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>39</volume><issue>5</issue><spage>869</spage><epage>873</epage><pages>869-873</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Human glyoxalase I (hGLO I) is a rate-limiting enzyme in the pathway for detoxification of apoptosis-inducible methylglyoxal (MG), which is the side product of tumor-specific aerobic glycolysis. GLO I has been reported to be overexpressed in various types of cancer cells, and has been expected as an attractive target for the development of new anticancer drugs. We previously discovered a novel inhibitor of hGLO I, named TLSC702, by our in silico screening method. Here, we show that TLSC702 inhibits the proliferation of human leukemia HL-60 cells and induces apoptosis in a dose-dependent manner. In addition, TLSC702 more significantly inhibits the proliferation of human lung cancer NCI-H522 cells, which highly express GLO I, than that of GLO I lower-expressing human lung cancer NCI-H460 cells. Furthermore, this antiproliferative effect of TLSC702 on NCI-H522 cells is in a dose- and time-dependent manner. These results suggest that TLSC702 can induce apoptosis in tumor cells by GLO I inhibition, which lead to accumulation of MG. 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| source | MEDLINE; J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | anticancer drug Antineoplastic Agents - pharmacology Apoptosis - drug effects Butyrates - pharmacology Cell Line, Tumor Cell Proliferation - drug effects DNA Fragmentation glyoxalase I Humans inhibitor Lactoylglutathione Lyase - antagonists & inhibitors Thiazoles - pharmacology |
| title | TLSC702, a Novel Inhibitor of Human Glyoxalase I, Induces Apoptosis in Tumor Cells |
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