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Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance
Background Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive. Methods A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients...
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| Published in: | Head & neck 2019-01, Vol.41 (1), p.185-197 |
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| cites | cdi_FETCH-LOGICAL-c4191-93f485052ac8548ddb04c949f7cbbbc18bebf11ad3071d31f80d8631cdcbec473 |
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| container_issue | 1 |
| container_start_page | 185 |
| container_title | Head & neck |
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| creator | Alam, Manzar Kashyap, Tanushree Mishra, Prajna Panda, Aditya K. Nagini, Siddavaram Mishra, Rajakishore |
| description | Background
Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive.
Methods
A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/cisplatin‐resistant oral tongue SCC (SCC9/SCC4‐CisR) cell line.
Results
Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(‐248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax‐dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4‐CisR cells.
Conclusion
Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin‐resistant human OSCC. |
| doi_str_mv | 10.1002/hed.25471 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2157644845</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2168617750</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4191-93f485052ac8548ddb04c949f7cbbbc18bebf11ad3071d31f80d8631cdcbec473</originalsourceid><addsrcrecordid>eNp1kEFLwzAUx4Mobk4PfgEJeNFDt6R5bdqjzumEgSB68lDSJJ0dbbMlLbpvb7bOi-DpPR4_fvzfH6FLSsaUkHDyqdU4jIDTIzSkJOUBYcCPdzuwgBEOA3Tm3IoQwmIIT9GAkQhSBjBEH6-m0lg0Clu97CrRlqbBpsBra8TarFvTlhLfi29c-rMVFXabTtSmc1jqqsJSWFk2phZ7hbLd0ntc6VrRSH2OTgpROX1xmCP0_jh7m86DxcvT8_RuEUigKQ1SVkASkSgUMokgUSonIFNICy7zPJc0yXVeUCqU_4QqRouEqCRmVCqZawmcjdBN7_WhN512bVaXbhdPNNonzUIa8Rgggcij13_Qlels49N5Kk5iynlEPHXbU9Ia56wusrUta2G3GSXZrvHMN57tG_fs1cHY5bW__pK_FXtg0gNfZaW3_5uy-eyhV_4A2sqKJw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2168617750</pqid></control><display><type>article</type><title>Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance</title><source>Wiley</source><creator>Alam, Manzar ; Kashyap, Tanushree ; Mishra, Prajna ; Panda, Aditya K. ; Nagini, Siddavaram ; Mishra, Rajakishore</creator><creatorcontrib>Alam, Manzar ; Kashyap, Tanushree ; Mishra, Prajna ; Panda, Aditya K. ; Nagini, Siddavaram ; Mishra, Rajakishore</creatorcontrib><description>Background
Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive.
Methods
A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/cisplatin‐resistant oral tongue SCC (SCC9/SCC4‐CisR) cell line.
Results
Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(‐248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax‐dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4‐CisR cells.
Conclusion
Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin‐resistant human OSCC.</description><identifier>ISSN: 1043-3074</identifier><identifier>ISSN: 1097-0347</identifier><identifier>EISSN: 1097-0347</identifier><identifier>DOI: 10.1002/hed.25471</identifier><identifier>PMID: 30549344</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adult ; Aged ; Akt ; AKT protein ; Antineoplastic Agents - pharmacology ; Apoptosis ; Bax ; BAX gene ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Bcl‐2 ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - therapy ; Cell death ; Cell Line, Tumor ; chemoradiation resistance ; Chemoradiotherapy ; Cisplatin ; Cisplatin - pharmacology ; Deoxyribonucleic acid ; Disease Progression ; DNA ; DNA methylation ; Drug resistance ; Drug Resistance, Neoplasm ; Female ; GSK3α ; GSK3β ; Head and neck ; Humans ; Limonins - pharmacology ; Male ; Middle Aged ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - pathology ; Mouth Neoplasms - therapy ; mRNA ; Oncogene Protein v-akt - metabolism ; Oral cancer ; Oral squamous cell carcinoma ; OSCC ; p53 ; p53 Protein ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; RNA, Messenger - metabolism ; Squamous cell carcinoma ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>Head & neck, 2019-01, Vol.41 (1), p.185-197</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4191-93f485052ac8548ddb04c949f7cbbbc18bebf11ad3071d31f80d8631cdcbec473</citedby><cites>FETCH-LOGICAL-c4191-93f485052ac8548ddb04c949f7cbbbc18bebf11ad3071d31f80d8631cdcbec473</cites><orcidid>0000-0002-1735-2411</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30549344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alam, Manzar</creatorcontrib><creatorcontrib>Kashyap, Tanushree</creatorcontrib><creatorcontrib>Mishra, Prajna</creatorcontrib><creatorcontrib>Panda, Aditya K.</creatorcontrib><creatorcontrib>Nagini, Siddavaram</creatorcontrib><creatorcontrib>Mishra, Rajakishore</creatorcontrib><title>Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance</title><title>Head & neck</title><addtitle>Head Neck</addtitle><description>Background
Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive.
Methods
A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/cisplatin‐resistant oral tongue SCC (SCC9/SCC4‐CisR) cell line.
Results
Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(‐248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax‐dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4‐CisR cells.
Conclusion
Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin‐resistant human OSCC.</description><subject>Adult</subject><subject>Aged</subject><subject>Akt</subject><subject>AKT protein</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Bax</subject><subject>BAX gene</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Bcl‐2</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - therapy</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>chemoradiation resistance</subject><subject>Chemoradiotherapy</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Deoxyribonucleic acid</subject><subject>Disease Progression</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>GSK3α</subject><subject>GSK3β</subject><subject>Head and neck</subject><subject>Humans</subject><subject>Limonins - pharmacology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Mouth Neoplasms - pathology</subject><subject>Mouth Neoplasms - therapy</subject><subject>mRNA</subject><subject>Oncogene Protein v-akt - metabolism</subject><subject>Oral cancer</subject><subject>Oral squamous cell carcinoma</subject><subject>OSCC</subject><subject>p53</subject><subject>p53 Protein</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Promoter Regions, Genetic</subject><subject>RNA, Messenger - metabolism</subject><subject>Squamous cell carcinoma</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>1043-3074</issn><issn>1097-0347</issn><issn>1097-0347</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kEFLwzAUx4Mobk4PfgEJeNFDt6R5bdqjzumEgSB68lDSJJ0dbbMlLbpvb7bOi-DpPR4_fvzfH6FLSsaUkHDyqdU4jIDTIzSkJOUBYcCPdzuwgBEOA3Tm3IoQwmIIT9GAkQhSBjBEH6-m0lg0Clu97CrRlqbBpsBra8TarFvTlhLfi29c-rMVFXabTtSmc1jqqsJSWFk2phZ7hbLd0ntc6VrRSH2OTgpROX1xmCP0_jh7m86DxcvT8_RuEUigKQ1SVkASkSgUMokgUSonIFNICy7zPJc0yXVeUCqU_4QqRouEqCRmVCqZawmcjdBN7_WhN512bVaXbhdPNNonzUIa8Rgggcij13_Qlels49N5Kk5iynlEPHXbU9Ia56wusrUta2G3GSXZrvHMN57tG_fs1cHY5bW__pK_FXtg0gNfZaW3_5uy-eyhV_4A2sqKJw</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Alam, Manzar</creator><creator>Kashyap, Tanushree</creator><creator>Mishra, Prajna</creator><creator>Panda, Aditya K.</creator><creator>Nagini, Siddavaram</creator><creator>Mishra, Rajakishore</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</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>7TK</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1735-2411</orcidid></search><sort><creationdate>201901</creationdate><title>Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance</title><author>Alam, Manzar ; Kashyap, Tanushree ; Mishra, Prajna ; Panda, Aditya K. ; Nagini, Siddavaram ; Mishra, Rajakishore</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4191-93f485052ac8548ddb04c949f7cbbbc18bebf11ad3071d31f80d8631cdcbec473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Akt</topic><topic>AKT protein</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Bax</topic><topic>BAX gene</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Bcl‐2</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - therapy</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>chemoradiation resistance</topic><topic>Chemoradiotherapy</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Deoxyribonucleic acid</topic><topic>Disease Progression</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>GSK3α</topic><topic>GSK3β</topic><topic>Head and neck</topic><topic>Humans</topic><topic>Limonins - pharmacology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Mouth Neoplasms - pathology</topic><topic>Mouth Neoplasms - therapy</topic><topic>mRNA</topic><topic>Oncogene Protein v-akt - metabolism</topic><topic>Oral cancer</topic><topic>Oral squamous cell carcinoma</topic><topic>OSCC</topic><topic>p53</topic><topic>p53 Protein</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Promoter Regions, Genetic</topic><topic>RNA, Messenger - metabolism</topic><topic>Squamous cell carcinoma</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alam, Manzar</creatorcontrib><creatorcontrib>Kashyap, Tanushree</creatorcontrib><creatorcontrib>Mishra, Prajna</creatorcontrib><creatorcontrib>Panda, Aditya K.</creatorcontrib><creatorcontrib>Nagini, Siddavaram</creatorcontrib><creatorcontrib>Mishra, Rajakishore</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>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Head & neck</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alam, Manzar</au><au>Kashyap, Tanushree</au><au>Mishra, Prajna</au><au>Panda, Aditya K.</au><au>Nagini, Siddavaram</au><au>Mishra, Rajakishore</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance</atitle><jtitle>Head & neck</jtitle><addtitle>Head Neck</addtitle><date>2019-01</date><risdate>2019</risdate><volume>41</volume><issue>1</issue><spage>185</spage><epage>197</epage><pages>185-197</pages><issn>1043-3074</issn><issn>1097-0347</issn><eissn>1097-0347</eissn><abstract>Background
Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive.
Methods
A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/cisplatin‐resistant oral tongue SCC (SCC9/SCC4‐CisR) cell line.
Results
Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(‐248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax‐dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4‐CisR cells.
Conclusion
Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin‐resistant human OSCC.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30549344</pmid><doi>10.1002/hed.25471</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-1735-2411</orcidid></addata></record> |
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| subjects | Adult Aged Akt AKT protein Antineoplastic Agents - pharmacology Apoptosis Bax BAX gene bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Bcl‐2 Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - therapy Cell death Cell Line, Tumor chemoradiation resistance Chemoradiotherapy Cisplatin Cisplatin - pharmacology Deoxyribonucleic acid Disease Progression DNA DNA methylation Drug resistance Drug Resistance, Neoplasm Female GSK3α GSK3β Head and neck Humans Limonins - pharmacology Male Middle Aged Mouth Neoplasms - metabolism Mouth Neoplasms - pathology Mouth Neoplasms - therapy mRNA Oncogene Protein v-akt - metabolism Oral cancer Oral squamous cell carcinoma OSCC p53 p53 Protein Polymorphism, Single Nucleotide Promoter Regions, Genetic RNA, Messenger - metabolism Squamous cell carcinoma Tumor Suppressor Protein p53 - metabolism |
| title | Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance |
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