Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma
Arecoline, the major alkaloid of areca nut, has been shown to cause strong genotoxicity and is considered a potential carcinogen. However, the detailed mechanism for arecoline‐induced carcinogenesis remains obscure. In this study, we noticed that the levels of p21 and p27 increased in two oral squam...
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| Veröffentlicht in: | Cancer science 2012-07, Vol.103 (7), p.1221-1229 |
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| creator | Ji, Wen‐Tsai Yang, Sheng‐Ru Chen, Jeff Yi‐Fu Cheng, Ya‐Ping Lee, Ying‐Ray Chiang, Ming‐Ko Chen, Hau‐Ren |
| description | Arecoline, the major alkaloid of areca nut, has been shown to cause strong genotoxicity and is considered a potential carcinogen. However, the detailed mechanism for arecoline‐induced carcinogenesis remains obscure. In this study, we noticed that the levels of p21 and p27 increased in two oral squamous cell carcinoma cell lines with high confluence. Furthermore, when treated with arecoline, elevated levels of p21 and p27 could be downregulated through the reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway. Although arecoline decreased the activity of mTORC1, the amounts of autophagosome‐like vacuoles or type II LC3 remained unchanged, suggesting that the downregulation of p21 and p27 was independent of autophagy‐mediated protein destruction. Arecoline also caused DNA damage through ROS, indicating that the reduced levels of p21 and p27 might facilitate G
1/S transition of the cell cycle and subsequently lead to error‐prone DNA replication. In conclusion, these data have provided a possible mechanism for arecoline‐induced carcinogenesis in subcytolytic doses in vivo. (Cancer Sci 2012; 103: 1221–1229) |
| doi_str_mv | 10.1111/j.1349-7006.2012.02294.x |
| format | Article |
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1/S transition of the cell cycle and subsequently lead to error‐prone DNA replication. In conclusion, these data have provided a possible mechanism for arecoline‐induced carcinogenesis in subcytolytic doses in vivo. (Cancer Sci 2012; 103: 1221–1229)</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/j.1349-7006.2012.02294.x</identifier><identifier>PMID: 22469187</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>Alkaloids ; Arecoline - pharmacology ; Blotting, Western ; Carcinogenesis ; Carcinogens ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell cycle ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cholinergic Agonists - pharmacology ; Cyclin-Dependent Kinase Inhibitor p21 - genetics ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; Cyclin-Dependent Kinase Inhibitor p27 - genetics ; Cyclin-Dependent Kinase Inhibitor p27 - metabolism ; Data processing ; DNA biosynthesis ; DNA Damage ; Down-Regulation - drug effects ; G1 Phase Cell Cycle Checkpoints - drug effects ; G2 Phase Cell Cycle Checkpoints - drug effects ; Genotoxicity ; Humans ; Male ; Mechanistic Target of Rapamycin Complex 1 ; Microscopy, Fluorescence ; Mouth Neoplasms - genetics ; Mouth Neoplasms - metabolism ; Multiprotein Complexes - genetics ; Multiprotein Complexes - metabolism ; oral squamous cell carcinoma ; Original ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Replication ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction - drug effects ; TOR protein ; TOR Serine-Threonine Kinases - genetics ; TOR Serine-Threonine Kinases - metabolism ; Tumor cell lines ; Vacuoles</subject><ispartof>Cancer science, 2012-07, Vol.103 (7), p.1221-1229</ispartof><rights>2012 Japanese Cancer Association</rights><rights>2012 Japanese Cancer Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659358/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659358/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1349-7006.2012.02294.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22469187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ji, Wen‐Tsai</creatorcontrib><creatorcontrib>Yang, Sheng‐Ru</creatorcontrib><creatorcontrib>Chen, Jeff Yi‐Fu</creatorcontrib><creatorcontrib>Cheng, Ya‐Ping</creatorcontrib><creatorcontrib>Lee, Ying‐Ray</creatorcontrib><creatorcontrib>Chiang, Ming‐Ko</creatorcontrib><creatorcontrib>Chen, Hau‐Ren</creatorcontrib><title>Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Arecoline, the major alkaloid of areca nut, has been shown to cause strong genotoxicity and is considered a potential carcinogen. However, the detailed mechanism for arecoline‐induced carcinogenesis remains obscure. In this study, we noticed that the levels of p21 and p27 increased in two oral squamous cell carcinoma cell lines with high confluence. Furthermore, when treated with arecoline, elevated levels of p21 and p27 could be downregulated through the reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway. Although arecoline decreased the activity of mTORC1, the amounts of autophagosome‐like vacuoles or type II LC3 remained unchanged, suggesting that the downregulation of p21 and p27 was independent of autophagy‐mediated protein destruction. Arecoline also caused DNA damage through ROS, indicating that the reduced levels of p21 and p27 might facilitate G
1/S transition of the cell cycle and subsequently lead to error‐prone DNA replication. In conclusion, these data have provided a possible mechanism for arecoline‐induced carcinogenesis in subcytolytic doses in vivo. (Cancer Sci 2012; 103: 1221–1229)</description><subject>Alkaloids</subject><subject>Arecoline - pharmacology</subject><subject>Blotting, Western</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cholinergic Agonists - pharmacology</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>Cyclin-Dependent Kinase Inhibitor p27 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</subject><subject>Data processing</subject><subject>DNA biosynthesis</subject><subject>DNA Damage</subject><subject>Down-Regulation - drug effects</subject><subject>G1 Phase Cell Cycle Checkpoints - drug effects</subject><subject>G2 Phase Cell Cycle Checkpoints - drug effects</subject><subject>Genotoxicity</subject><subject>Humans</subject><subject>Male</subject><subject>Mechanistic Target of Rapamycin Complex 1</subject><subject>Microscopy, Fluorescence</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Multiprotein Complexes - genetics</subject><subject>Multiprotein Complexes - metabolism</subject><subject>oral squamous cell carcinoma</subject><subject>Original</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Replication</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Signal Transduction - drug effects</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - genetics</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Tumor cell lines</subject><subject>Vacuoles</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkd1q3DAQhUVpaNJtX6Hosjd2JFleWRctLEubFAKBJr0Wsjy7q0W2HMnen2fJy0bepEs7N2fgDGdm-BDClOQ01fU2pwWXmSBknjNCWU4Ykzw_vENXZ-P9qReZJAW7RB9j3BJSzLnkH9AlY3wuaSWu0PMigPHOdoAbv-8CrEenB4jYwQ5cxH6Fe0ax7pqkAg-b4Mf1JingANoMdgfYH45r6HDswViI1-3j_W9sfNs7OGCKez1s9vp4imiTGt8NwdbjAHjw2AftcHwadevHiA04h40Oxna-1Z_QxUq7CJ_fdIb-_PzxuLzN7u5vfi0Xd9mWy4JnBkoiuCGFJITIVaMl0KpuZPrRVFKUlJec04pLvapE3RhCdDUvZSMEqzkpRDFD319z-7FuoTGQDtRO9cG2OhyV11b973R2o9Z-p0SKKcoqBXx9Cwj-aYQ4qNbG6RfdQXpL0YSgSqekbTP05d9d5yV_iaSBb68De-vgePYpURN5tVUTYDUBVhN5dSKvDmq5eJi64gVA46QD</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Ji, Wen‐Tsai</creator><creator>Yang, Sheng‐Ru</creator><creator>Chen, Jeff Yi‐Fu</creator><creator>Cheng, Ya‐Ping</creator><creator>Lee, Ying‐Ray</creator><creator>Chiang, Ming‐Ko</creator><creator>Chen, Hau‐Ren</creator><general>John Wiley and Sons Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201207</creationdate><title>Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma</title><author>Ji, Wen‐Tsai ; Yang, Sheng‐Ru ; Chen, Jeff Yi‐Fu ; Cheng, Ya‐Ping ; Lee, Ying‐Ray ; Chiang, Ming‐Ko ; Chen, Hau‐Ren</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j4934-ce5074c0390009fda9e18bd9246c8975145441849af87bdc00a8659d772b40373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Alkaloids</topic><topic>Arecoline - pharmacology</topic><topic>Blotting, Western</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cholinergic Agonists - pharmacology</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>Cyclin-Dependent Kinase Inhibitor p27 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</topic><topic>Data processing</topic><topic>DNA biosynthesis</topic><topic>DNA Damage</topic><topic>Down-Regulation - drug effects</topic><topic>G1 Phase Cell Cycle Checkpoints - drug effects</topic><topic>G2 Phase Cell Cycle Checkpoints - drug effects</topic><topic>Genotoxicity</topic><topic>Humans</topic><topic>Male</topic><topic>Mechanistic Target of Rapamycin Complex 1</topic><topic>Microscopy, Fluorescence</topic><topic>Mouth Neoplasms - genetics</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Multiprotein Complexes - genetics</topic><topic>Multiprotein Complexes - metabolism</topic><topic>oral squamous cell carcinoma</topic><topic>Original</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Replication</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Signal Transduction - drug effects</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - genetics</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Tumor cell lines</topic><topic>Vacuoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ji, Wen‐Tsai</creatorcontrib><creatorcontrib>Yang, Sheng‐Ru</creatorcontrib><creatorcontrib>Chen, Jeff Yi‐Fu</creatorcontrib><creatorcontrib>Cheng, Ya‐Ping</creatorcontrib><creatorcontrib>Lee, Ying‐Ray</creatorcontrib><creatorcontrib>Chiang, Ming‐Ko</creatorcontrib><creatorcontrib>Chen, Hau‐Ren</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Ji, Wen‐Tsai</au><au>Yang, Sheng‐Ru</au><au>Chen, Jeff Yi‐Fu</au><au>Cheng, Ya‐Ping</au><au>Lee, Ying‐Ray</au><au>Chiang, Ming‐Ko</au><au>Chen, Hau‐Ren</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2012-07</date><risdate>2012</risdate><volume>103</volume><issue>7</issue><spage>1221</spage><epage>1229</epage><pages>1221-1229</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Arecoline, the major alkaloid of areca nut, has been shown to cause strong genotoxicity and is considered a potential carcinogen. However, the detailed mechanism for arecoline‐induced carcinogenesis remains obscure. In this study, we noticed that the levels of p21 and p27 increased in two oral squamous cell carcinoma cell lines with high confluence. Furthermore, when treated with arecoline, elevated levels of p21 and p27 could be downregulated through the reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway. Although arecoline decreased the activity of mTORC1, the amounts of autophagosome‐like vacuoles or type II LC3 remained unchanged, suggesting that the downregulation of p21 and p27 was independent of autophagy‐mediated protein destruction. Arecoline also caused DNA damage through ROS, indicating that the reduced levels of p21 and p27 might facilitate G
1/S transition of the cell cycle and subsequently lead to error‐prone DNA replication. In conclusion, these data have provided a possible mechanism for arecoline‐induced carcinogenesis in subcytolytic doses in vivo. (Cancer Sci 2012; 103: 1221–1229)</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>22469187</pmid><doi>10.1111/j.1349-7006.2012.02294.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alkaloids Arecoline - pharmacology Blotting, Western Carcinogenesis Carcinogens Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell cycle Cell Line, Tumor Cell Proliferation - drug effects Cholinergic Agonists - pharmacology Cyclin-Dependent Kinase Inhibitor p21 - genetics Cyclin-Dependent Kinase Inhibitor p21 - metabolism Cyclin-Dependent Kinase Inhibitor p27 - genetics Cyclin-Dependent Kinase Inhibitor p27 - metabolism Data processing DNA biosynthesis DNA Damage Down-Regulation - drug effects G1 Phase Cell Cycle Checkpoints - drug effects G2 Phase Cell Cycle Checkpoints - drug effects Genotoxicity Humans Male Mechanistic Target of Rapamycin Complex 1 Microscopy, Fluorescence Mouth Neoplasms - genetics Mouth Neoplasms - metabolism Multiprotein Complexes - genetics Multiprotein Complexes - metabolism oral squamous cell carcinoma Original Reactive oxygen species Reactive Oxygen Species - metabolism Replication Reverse Transcriptase Polymerase Chain Reaction Signal Transduction - drug effects TOR protein TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism Tumor cell lines Vacuoles |
| title | Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma |
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