Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer
Abstract Cervical cancer still remains a major health problem in women worldwide. Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues a...
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| Veröffentlicht in: | Cancer letters 2009-02, Vol.274 (1), p.47-53 |
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| creator | Liu, Youqing Xing, Hui Weng, Danhui Song, Xiaohong Qin, Xiaomin Xia, Xi Weng, Yanjie Liang, Fengqi Chen, Gang Han, Xiaobing Ma, Xiaoli Wang, Shixuan Zhou, Jianfeng Xu, Gang Meng, Li Ma, Ding |
| description | Abstract Cervical cancer still remains a major health problem in women worldwide. Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues and is converted to form the active metabolite SN-38. The study tried to explore the in vitro mechanisms of apoptosis induced by SN-38 in cervical cancer cell lines HeLa and SiHa. The results demonstrated here that SN-38 inhibited cell proliferation in a time- and dose-dependant manner. Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt. |
| doi_str_mv | 10.1016/j.canlet.2008.08.037 |
| format | Article |
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Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues and is converted to form the active metabolite SN-38. The study tried to explore the in vitro mechanisms of apoptosis induced by SN-38 in cervical cancer cell lines HeLa and SiHa. The results demonstrated here that SN-38 inhibited cell proliferation in a time- and dose-dependant manner. Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2008.08.037</identifier><identifier>PMID: 18929442</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Akt1 ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Blotting, Western ; Camptothecin - analogs & derivatives ; Camptothecin - pharmacology ; Cancer therapies ; Cell culture ; Cell Proliferation - drug effects ; Cervical cancer ; Cloning ; Cyclin-dependent kinases ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA damage ; Enzymes ; Female ; Flow Cytometry ; Gene expression ; Hematology, Oncology and Palliative Medicine ; Humans ; Kinases ; p53 ; Phosphorylation ; Protein expression ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction - drug effects ; SN-38 ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53 - metabolism ; Uterine Cervical Neoplasms - metabolism ; Uterine Cervical Neoplasms - pathology</subject><ispartof>Cancer letters, 2009-02, Vol.274 (1), p.47-53</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2008 Elsevier Ireland Ltd</rights><rights>Copyright Elsevier Limited Feb 8, 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-a47cd125297d9928c5b49e58bac88e354f12da0f8eb68d202b90cb1f7d577cba3</citedby><cites>FETCH-LOGICAL-c540t-a47cd125297d9928c5b49e58bac88e354f12da0f8eb68d202b90cb1f7d577cba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2008.08.037$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18929442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Youqing</creatorcontrib><creatorcontrib>Xing, Hui</creatorcontrib><creatorcontrib>Weng, Danhui</creatorcontrib><creatorcontrib>Song, Xiaohong</creatorcontrib><creatorcontrib>Qin, Xiaomin</creatorcontrib><creatorcontrib>Xia, Xi</creatorcontrib><creatorcontrib>Weng, Yanjie</creatorcontrib><creatorcontrib>Liang, Fengqi</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Han, Xiaobing</creatorcontrib><creatorcontrib>Ma, Xiaoli</creatorcontrib><creatorcontrib>Wang, Shixuan</creatorcontrib><creatorcontrib>Zhou, Jianfeng</creatorcontrib><creatorcontrib>Xu, Gang</creatorcontrib><creatorcontrib>Meng, Li</creatorcontrib><creatorcontrib>Ma, Ding</creatorcontrib><title>Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract Cervical cancer still remains a major health problem in women worldwide. Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues and is converted to form the active metabolite SN-38. The study tried to explore the in vitro mechanisms of apoptosis induced by SN-38 in cervical cancer cell lines HeLa and SiHa. The results demonstrated here that SN-38 inhibited cell proliferation in a time- and dose-dependant manner. Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt.</description><subject>Akt1</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Blotting, Western</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - pharmacology</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Cell Proliferation - drug effects</subject><subject>Cervical cancer</subject><subject>Cloning</subject><subject>Cyclin-dependent kinases</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Enzymes</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Gene expression</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Kinases</subject><subject>p53</subject><subject>Phosphorylation</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>SN-38</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Uterine Cervical Neoplasms - metabolism</subject><subject>Uterine Cervical Neoplasms - pathology</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9r3DAQxUVpSbZpvkEpgkJv3o7-WdKlEEKTLoT2kPYsZHmcauO1tpYd2G9fmV0I5BIYkBC_eZLeG0I-MlgzYPXX7Tr4ocdpzQHMeimh35AVM5pX2hp4S1YgQFbCCHVO3ue8BQAltToj58xYbqXkK7LZDH9jE6eYBpo6evU40RwfBt_H4YE2B3r_swjQOLRzwEz9Pu2nlGMuJzTg-BSD72l5R9l_IO8632e8PK0X5M_N99_XP6q7X7eb66u7KigJU-WlDi3jilvdWstNUI20qEzjgzEolOwYbz10BpvatBx4YyE0rNOt0jo0XlyQL0fd_Zj-zZgnt4s5YN_7AdOcXV3r2mpuXgU5CGGBiwJ-fgFu0zwWD7JjarHMcq0LJY9UGFPOI3ZuP8adHw-OgVsScVt3TMQtibilxNL26SQ-Nztsn5tOERTg2xHAYtpTxNHlELE42sYRw-TaFF-74aVAKOktyTziAfPzX1zmDtz9MhXLUIAB0KBr8R9y07Fl</recordid><startdate>20090208</startdate><enddate>20090208</enddate><creator>Liu, Youqing</creator><creator>Xing, Hui</creator><creator>Weng, Danhui</creator><creator>Song, Xiaohong</creator><creator>Qin, Xiaomin</creator><creator>Xia, Xi</creator><creator>Weng, Yanjie</creator><creator>Liang, Fengqi</creator><creator>Chen, Gang</creator><creator>Han, Xiaobing</creator><creator>Ma, Xiaoli</creator><creator>Wang, Shixuan</creator><creator>Zhou, Jianfeng</creator><creator>Xu, Gang</creator><creator>Meng, Li</creator><creator>Ma, Ding</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20090208</creationdate><title>Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer</title><author>Liu, Youqing ; Xing, Hui ; Weng, Danhui ; Song, Xiaohong ; Qin, Xiaomin ; Xia, Xi ; Weng, Yanjie ; Liang, Fengqi ; Chen, Gang ; Han, Xiaobing ; Ma, Xiaoli ; Wang, Shixuan ; Zhou, Jianfeng ; Xu, Gang ; Meng, Li ; Ma, Ding</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-a47cd125297d9928c5b49e58bac88e354f12da0f8eb68d202b90cb1f7d577cba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Akt1</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Blotting, Western</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - pharmacology</topic><topic>Cancer therapies</topic><topic>Cell culture</topic><topic>Cell Proliferation - drug effects</topic><topic>Cervical cancer</topic><topic>Cloning</topic><topic>Cyclin-dependent kinases</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>Enzymes</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Gene expression</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Kinases</topic><topic>p53</topic><topic>Phosphorylation</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>SN-38</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Uterine Cervical Neoplasms - metabolism</topic><topic>Uterine Cervical Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Youqing</creatorcontrib><creatorcontrib>Xing, Hui</creatorcontrib><creatorcontrib>Weng, Danhui</creatorcontrib><creatorcontrib>Song, Xiaohong</creatorcontrib><creatorcontrib>Qin, Xiaomin</creatorcontrib><creatorcontrib>Xia, Xi</creatorcontrib><creatorcontrib>Weng, Yanjie</creatorcontrib><creatorcontrib>Liang, Fengqi</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Han, Xiaobing</creatorcontrib><creatorcontrib>Ma, Xiaoli</creatorcontrib><creatorcontrib>Wang, Shixuan</creatorcontrib><creatorcontrib>Zhou, Jianfeng</creatorcontrib><creatorcontrib>Xu, Gang</creatorcontrib><creatorcontrib>Meng, Li</creatorcontrib><creatorcontrib>Ma, Ding</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Youqing</au><au>Xing, Hui</au><au>Weng, Danhui</au><au>Song, Xiaohong</au><au>Qin, Xiaomin</au><au>Xia, Xi</au><au>Weng, Yanjie</au><au>Liang, Fengqi</au><au>Chen, Gang</au><au>Han, Xiaobing</au><au>Ma, Xiaoli</au><au>Wang, Shixuan</au><au>Zhou, Jianfeng</au><au>Xu, Gang</au><au>Meng, Li</au><au>Ma, Ding</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2009-02-08</date><risdate>2009</risdate><volume>274</volume><issue>1</issue><spage>47</spage><epage>53</epage><pages>47-53</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract Cervical cancer still remains a major health problem in women worldwide. Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues and is converted to form the active metabolite SN-38. The study tried to explore the in vitro mechanisms of apoptosis induced by SN-38 in cervical cancer cell lines HeLa and SiHa. The results demonstrated here that SN-38 inhibited cell proliferation in a time- and dose-dependant manner. Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18929442</pmid><doi>10.1016/j.canlet.2008.08.037</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Akt1 Antineoplastic Agents, Phytogenic - pharmacology Apoptosis Apoptosis - drug effects Blotting, Western Camptothecin - analogs & derivatives Camptothecin - pharmacology Cancer therapies Cell culture Cell Proliferation - drug effects Cervical cancer Cloning Cyclin-dependent kinases Cytotoxicity Deoxyribonucleic acid DNA DNA damage Enzymes Female Flow Cytometry Gene expression Hematology, Oncology and Palliative Medicine Humans Kinases p53 Phosphorylation Protein expression Proteins Proto-Oncogene Proteins c-akt - metabolism Signal Transduction - drug effects SN-38 Tumor Cells, Cultured Tumor Suppressor Protein p53 - metabolism Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - pathology |
| title | Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer |
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