Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum (II) in oral cancer cell lines
The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sen...
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| Veröffentlicht in: | Oral oncology 2005-11, Vol.41 (10), p.984-993 |
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| creator | MAKI, Yu MURAKAMI, Jun TANAKA, Noriaki MATSUBARA, Nagahide KISHI, Kanji ASAUMI, Jun-Ichi TSUJIGIWA, Hidetsugu NAGATSUKA, Hitoshi KOKEGUCHI, Susumu FUKUI, Kazuhiro KAWAI, Noriko YANAGI, Yoshinobu KURODA, Masahiro |
| description | The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell lines. CDDP depleted MGMT protein and mRNA levels in all four cell lines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine and CDDP, whereas two other cell lines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O6-benzylguanine (O6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy. |
| doi_str_mv | 10.1016/j.oraloncology.2005.05.011 |
| format | Article |
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However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell lines. CDDP depleted MGMT protein and mRNA levels in all four cell lines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine and CDDP, whereas two other cell lines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O6-benzylguanine (O6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O6-BG. 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Stomatology ; Taxoids - administration & dosage ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><ispartof>Oral oncology, 2005-11, Vol.41 (10), p.984-993</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2441-114a6396b3a336138f1d29353df1bd9bf073bb1230e5fb4b8b11dd2c3e2ed9023</citedby><cites>FETCH-LOGICAL-c2441-114a6396b3a336138f1d29353df1bd9bf073bb1230e5fb4b8b11dd2c3e2ed9023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17194954$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16043385$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MAKI, Yu</creatorcontrib><creatorcontrib>MURAKAMI, Jun</creatorcontrib><creatorcontrib>TANAKA, Noriaki</creatorcontrib><creatorcontrib>MATSUBARA, Nagahide</creatorcontrib><creatorcontrib>KISHI, Kanji</creatorcontrib><creatorcontrib>ASAUMI, Jun-Ichi</creatorcontrib><creatorcontrib>TSUJIGIWA, Hidetsugu</creatorcontrib><creatorcontrib>NAGATSUKA, Hitoshi</creatorcontrib><creatorcontrib>KOKEGUCHI, Susumu</creatorcontrib><creatorcontrib>FUKUI, Kazuhiro</creatorcontrib><creatorcontrib>KAWAI, Noriko</creatorcontrib><creatorcontrib>YANAGI, Yoshinobu</creatorcontrib><creatorcontrib>KURODA, Masahiro</creatorcontrib><title>Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum (II) in oral cancer cell lines</title><title>Oral oncology</title><addtitle>Oral Oncol</addtitle><description>The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell lines. CDDP depleted MGMT protein and mRNA levels in all four cell lines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine and CDDP, whereas two other cell lines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O6-benzylguanine (O6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy.</description><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor - drug effects</subject><subject>Cisplatin - administration & dosage</subject><subject>Cisplatin - antagonists & inhibitors</subject><subject>DNA Repair</subject><subject>Drug Resistance, Neoplasm</subject><subject>Guanine - analogs & derivatives</subject><subject>Guanine - metabolism</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Methylnitronitrosoguanidine - therapeutic use</subject><subject>Mouth Neoplasms - drug therapy</subject><subject>Mouth Neoplasms - enzymology</subject><subject>O-Methylguanine-DNA Methyltransferase - drug effects</subject><subject>O-Methylguanine-DNA Methyltransferase - metabolism</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Taxoids - administration & dosage</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>1368-8375</issn><issn>1879-0593</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkV2L1DAUhoso7of-BQmCohcdc5I2bfduWVcdWFwQvQ753MmQJmOSCuMP8nfaMsUVDiQcnjfJyVNVrwFvAAP7sN_EJHwMKvr4cNwQjNvNUgBPqnPou6HG7UCfznvK-rqnXXtWXeS8xzMILX5enQHDDaV9e179-Ra9QdGie1aPpuyO_mESwQVTf_x6jU6dkkTI1iSRDRJBI2OtUWUNSRN-_wuhGFDZLVRxdZnGmJBQxf1y5bjgyuVaOzHOpHZq52OKBy-KC9OI3m2375ELaBkNKRGUSUgZ75Gf6fyiemaFz-blul5WPz7dfr_5Ut_df97eXN_VijQN1ACNYHRgkgpKGdDegiYDbam2IPUgLe6olEAoNq2VjewlgNZEUUOMHjChl9Xb07mHFH9OJhc-urw8QwQTp8xZzwZCOjaDVydQpZhzMpYfkhtFOnLAfLHE9_x_S3yxxJcCmMOv1lsmORr9GF21zMCbFRBZCW9nAfPfPXIdDM3QNvQvE1OiVQ</recordid><startdate>200511</startdate><enddate>200511</enddate><creator>MAKI, Yu</creator><creator>MURAKAMI, Jun</creator><creator>TANAKA, Noriaki</creator><creator>MATSUBARA, Nagahide</creator><creator>KISHI, Kanji</creator><creator>ASAUMI, Jun-Ichi</creator><creator>TSUJIGIWA, Hidetsugu</creator><creator>NAGATSUKA, Hitoshi</creator><creator>KOKEGUCHI, Susumu</creator><creator>FUKUI, Kazuhiro</creator><creator>KAWAI, Noriko</creator><creator>YANAGI, Yoshinobu</creator><creator>KURODA, Masahiro</creator><general>Elsevier</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>200511</creationdate><title>Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum (II) in oral cancer cell lines</title><author>MAKI, Yu ; MURAKAMI, Jun ; TANAKA, Noriaki ; MATSUBARA, Nagahide ; KISHI, Kanji ; ASAUMI, Jun-Ichi ; TSUJIGIWA, Hidetsugu ; NAGATSUKA, Hitoshi ; KOKEGUCHI, Susumu ; FUKUI, Kazuhiro ; KAWAI, Noriko ; YANAGI, Yoshinobu ; KURODA, Masahiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2441-114a6396b3a336138f1d29353df1bd9bf073bb1230e5fb4b8b11dd2c3e2ed9023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor - drug effects</topic><topic>Cisplatin - administration & dosage</topic><topic>Cisplatin - antagonists & inhibitors</topic><topic>DNA Repair</topic><topic>Drug Resistance, Neoplasm</topic><topic>Guanine - analogs & derivatives</topic><topic>Guanine - metabolism</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Methylnitronitrosoguanidine - therapeutic use</topic><topic>Mouth Neoplasms - drug therapy</topic><topic>Mouth Neoplasms - enzymology</topic><topic>O-Methylguanine-DNA Methyltransferase - drug effects</topic><topic>O-Methylguanine-DNA Methyltransferase - metabolism</topic><topic>Otorhinolaryngology. 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However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell lines. CDDP depleted MGMT protein and mRNA levels in all four cell lines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine and CDDP, whereas two other cell lines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O6-benzylguanine (O6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy.</abstract><cop>Oxford</cop><pub>Elsevier</pub><pmid>16043385</pmid><doi>10.1016/j.oraloncology.2005.05.011</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1368-8375 |
| ispartof | Oral oncology, 2005-11, Vol.41 (10), p.984-993 |
| issn | 1368-8375 1879-0593 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Antineoplastic Agents - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Cell Line, Tumor - drug effects Cisplatin - administration & dosage Cisplatin - antagonists & inhibitors DNA Repair Drug Resistance, Neoplasm Guanine - analogs & derivatives Guanine - metabolism Humans Medical sciences Methylnitronitrosoguanidine - therapeutic use Mouth Neoplasms - drug therapy Mouth Neoplasms - enzymology O-Methylguanine-DNA Methyltransferase - drug effects O-Methylguanine-DNA Methyltransferase - metabolism Otorhinolaryngology. Stomatology Taxoids - administration & dosage Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology |
| title | Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum (II) in oral cancer cell lines |
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