Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization
Human hepatocellular carcinoma (HCC) remains incurable with current therapies, and novel biologically based therapies are urgently needed. Arsenic agents have long been used as anticancer agents in traditional Chinese medicine. In this study, to evaluate the effect of As 2 O 3 on HCC cells, we inves...
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| Veröffentlicht in: | Medical oncology (Northwood, London, England) London, England), 2009-06, Vol.26 (2), p.178-185 |
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| creator | Fei, Min Lu, Mudan Wang, You Zhao, Yueming He, Song Gao, Shangfeng Ke, Qing Liu, Yonghua Li, Peng Cui, Xiaopeng Shen, Aiguo Cheng, Chun |
| description | Human hepatocellular carcinoma (HCC) remains incurable with current therapies, and novel biologically based therapies are urgently needed. Arsenic agents have long been used as anticancer agents in traditional Chinese medicine. In this study, to evaluate the effect of As
2
O
3
on HCC cells, we investigate cell growth inhibition, cell cycle arrest, and the molecular mechanism after As
2
O
3
treatment in human HCC cells in vitro. We detected the proliferation of HCC cells by the Cell Counting Kit and FACS/Calibur Flow Cytometer and analyzed the expression and localization of FOXO3a by Western blotting Analysis and Cell Fractionation. Furthermore, we study the Akt activation after As
2
O
3
treatment and the HCC cells proliferation after combination of As
2
O
3
with PI3K inhibitor Wortmannin. As
2
O
3
significantly inhibited the proliferation of all the three HCC cell lines (SMMC7721, HepG2, Hep3B) tested in this study in a dose-dependent manner. Western blotting revealed that treatment HCC cells HepG2 with As
2
O
3
resulted in the increasing of FOXO3a expression and triggered phosphorylation of FOXO3a at the Thr
32
residue decrease. This FOXO3a accumulation correlated well with the As
2
O
3
-induced reduction of active Akt. Nuclear and cytoplasmic protein extracts isolated from the HCC cell line HepG2 revealed that the amount of nuclear FOXO3a was increased by treatment with As
2
O
3
, whereas the amount of cytoplasmic FOXO3a was decreased. Both As
2
O
3
and PI3K/Akt inhibitor Wortmannin induced cell cycle arrest. However, compared with As
2
O
3
alone, PI3K inhibitor Wortmannin combined with As
2
O
3
enhanced the antitumor effect of As
2
O
3
through induction of apoptosis. These findings suggest that As
2
O
3
at a clinically safe concentration may be an effective chemotherapeutic agent, and that As
2
O
3
and PI3K/Akt inhibitor Wortmannin may synergize for HCC cells. Taken together, the present study may suggest a specific molecular mechanism by which HCC cell lines are susceptible to the As
2
O
3
therapy through FOXO3a expression and localization. |
| doi_str_mv | 10.1007/s12032-008-9105-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67256671</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2393918531</sourcerecordid><originalsourceid>FETCH-LOGICAL-c435t-5cebbe6d9557f7815ca66f7369e2731d361bb7ef1647ba173935b411627cf7083</originalsourceid><addsrcrecordid>eNp1kcFq3DAQhkVJSdI0D9BLETnkplZjrTT2MYQmLQT20kJuQpblXQVb2kp2kiYvX5ldCBR6khh9882In5BPwL8A5_g1Q8VFxTivWQNcsvodOQUpGwYC7o_KXUhkXCp-Qj7k_MB5BbJqjskJ1I1Ajs0peb1K2QVv6ZR8fPadYz50s3Ud3aT4NG2pScnlicaebufRBLp1OzNF64ZhHkyi1iTrQxwNXUqZ-vAYh0cfNvRmfb8WhrrnXRFkHwM1oaNDtGbwL2YqhY_kfW-G7M4P5xn5dfPt5_V3dre-_XF9dcfsSsiJSeva1qmukRJ7rEFao1SPQjWuQgGdUNC26HpQK2wNoGiEbFcAqkLbI6_FGbnce3cp_p7Lb_To87KuCS7OWSuspFIIBbz4B3yIcwplN12jlAIAFxvsIZtizsn1epf8aNIfDVwvseh9LLrEopdY9NLz-SCe29F1bx2HHApQ7YFcnsLGpbfJ_7f-BS6umZY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>875531178</pqid></control><display><type>article</type><title>Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Fei, Min ; Lu, Mudan ; Wang, You ; Zhao, Yueming ; He, Song ; Gao, Shangfeng ; Ke, Qing ; Liu, Yonghua ; Li, Peng ; Cui, Xiaopeng ; Shen, Aiguo ; Cheng, Chun</creator><creatorcontrib>Fei, Min ; Lu, Mudan ; Wang, You ; Zhao, Yueming ; He, Song ; Gao, Shangfeng ; Ke, Qing ; Liu, Yonghua ; Li, Peng ; Cui, Xiaopeng ; Shen, Aiguo ; Cheng, Chun</creatorcontrib><description>Human hepatocellular carcinoma (HCC) remains incurable with current therapies, and novel biologically based therapies are urgently needed. Arsenic agents have long been used as anticancer agents in traditional Chinese medicine. In this study, to evaluate the effect of As
2
O
3
on HCC cells, we investigate cell growth inhibition, cell cycle arrest, and the molecular mechanism after As
2
O
3
treatment in human HCC cells in vitro. We detected the proliferation of HCC cells by the Cell Counting Kit and FACS/Calibur Flow Cytometer and analyzed the expression and localization of FOXO3a by Western blotting Analysis and Cell Fractionation. Furthermore, we study the Akt activation after As
2
O
3
treatment and the HCC cells proliferation after combination of As
2
O
3
with PI3K inhibitor Wortmannin. As
2
O
3
significantly inhibited the proliferation of all the three HCC cell lines (SMMC7721, HepG2, Hep3B) tested in this study in a dose-dependent manner. Western blotting revealed that treatment HCC cells HepG2 with As
2
O
3
resulted in the increasing of FOXO3a expression and triggered phosphorylation of FOXO3a at the Thr
32
residue decrease. This FOXO3a accumulation correlated well with the As
2
O
3
-induced reduction of active Akt. Nuclear and cytoplasmic protein extracts isolated from the HCC cell line HepG2 revealed that the amount of nuclear FOXO3a was increased by treatment with As
2
O
3
, whereas the amount of cytoplasmic FOXO3a was decreased. Both As
2
O
3
and PI3K/Akt inhibitor Wortmannin induced cell cycle arrest. However, compared with As
2
O
3
alone, PI3K inhibitor Wortmannin combined with As
2
O
3
enhanced the antitumor effect of As
2
O
3
through induction of apoptosis. These findings suggest that As
2
O
3
at a clinically safe concentration may be an effective chemotherapeutic agent, and that As
2
O
3
and PI3K/Akt inhibitor Wortmannin may synergize for HCC cells. Taken together, the present study may suggest a specific molecular mechanism by which HCC cell lines are susceptible to the As
2
O
3
therapy through FOXO3a expression and localization.</description><identifier>ISSN: 1357-0560</identifier><identifier>EISSN: 1559-131X</identifier><identifier>DOI: 10.1007/s12032-008-9105-8</identifier><identifier>PMID: 18937079</identifier><identifier>CODEN: MONCEZ</identifier><language>eng</language><publisher>New York: Humana Press Inc</publisher><subject>Androstadienes - pharmacology ; Antineoplastic Agents - therapeutic use ; Arsenicals - therapeutic use ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - enzymology ; Carcinoma, Hepatocellular - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Forkhead Box Protein O3 ; Forkhead Transcription Factors - analysis ; Forkhead Transcription Factors - metabolism ; Hematology ; Humans ; Internal Medicine ; Liver Neoplasms - drug therapy ; Liver Neoplasms - enzymology ; Liver Neoplasms - metabolism ; Medicine ; Medicine & Public Health ; Metabolic Networks and Pathways - drug effects ; Oncology ; Original Paper ; Oxides - therapeutic use ; Pathology ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism</subject><ispartof>Medical oncology (Northwood, London, England), 2009-06, Vol.26 (2), p.178-185</ispartof><rights>Humana Press Inc. 2008</rights><rights>Humana Press Inc. 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-5cebbe6d9557f7815ca66f7369e2731d361bb7ef1647ba173935b411627cf7083</citedby><cites>FETCH-LOGICAL-c435t-5cebbe6d9557f7815ca66f7369e2731d361bb7ef1647ba173935b411627cf7083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12032-008-9105-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12032-008-9105-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18937079$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fei, Min</creatorcontrib><creatorcontrib>Lu, Mudan</creatorcontrib><creatorcontrib>Wang, You</creatorcontrib><creatorcontrib>Zhao, Yueming</creatorcontrib><creatorcontrib>He, Song</creatorcontrib><creatorcontrib>Gao, Shangfeng</creatorcontrib><creatorcontrib>Ke, Qing</creatorcontrib><creatorcontrib>Liu, Yonghua</creatorcontrib><creatorcontrib>Li, Peng</creatorcontrib><creatorcontrib>Cui, Xiaopeng</creatorcontrib><creatorcontrib>Shen, Aiguo</creatorcontrib><creatorcontrib>Cheng, Chun</creatorcontrib><title>Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization</title><title>Medical oncology (Northwood, London, England)</title><addtitle>Med Oncol</addtitle><addtitle>Med Oncol</addtitle><description>Human hepatocellular carcinoma (HCC) remains incurable with current therapies, and novel biologically based therapies are urgently needed. Arsenic agents have long been used as anticancer agents in traditional Chinese medicine. In this study, to evaluate the effect of As
2
O
3
on HCC cells, we investigate cell growth inhibition, cell cycle arrest, and the molecular mechanism after As
2
O
3
treatment in human HCC cells in vitro. We detected the proliferation of HCC cells by the Cell Counting Kit and FACS/Calibur Flow Cytometer and analyzed the expression and localization of FOXO3a by Western blotting Analysis and Cell Fractionation. Furthermore, we study the Akt activation after As
2
O
3
treatment and the HCC cells proliferation after combination of As
2
O
3
with PI3K inhibitor Wortmannin. As
2
O
3
significantly inhibited the proliferation of all the three HCC cell lines (SMMC7721, HepG2, Hep3B) tested in this study in a dose-dependent manner. Western blotting revealed that treatment HCC cells HepG2 with As
2
O
3
resulted in the increasing of FOXO3a expression and triggered phosphorylation of FOXO3a at the Thr
32
residue decrease. This FOXO3a accumulation correlated well with the As
2
O
3
-induced reduction of active Akt. Nuclear and cytoplasmic protein extracts isolated from the HCC cell line HepG2 revealed that the amount of nuclear FOXO3a was increased by treatment with As
2
O
3
, whereas the amount of cytoplasmic FOXO3a was decreased. Both As
2
O
3
and PI3K/Akt inhibitor Wortmannin induced cell cycle arrest. However, compared with As
2
O
3
alone, PI3K inhibitor Wortmannin combined with As
2
O
3
enhanced the antitumor effect of As
2
O
3
through induction of apoptosis. These findings suggest that As
2
O
3
at a clinically safe concentration may be an effective chemotherapeutic agent, and that As
2
O
3
and PI3K/Akt inhibitor Wortmannin may synergize for HCC cells. Taken together, the present study may suggest a specific molecular mechanism by which HCC cell lines are susceptible to the As
2
O
3
therapy through FOXO3a expression and localization.</description><subject>Androstadienes - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Arsenicals - therapeutic use</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - enzymology</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Forkhead Box Protein O3</subject><subject>Forkhead Transcription Factors - analysis</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Hematology</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - enzymology</subject><subject>Liver Neoplasms - metabolism</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Networks and Pathways - drug effects</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Oxides - therapeutic use</subject><subject>Pathology</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><issn>1357-0560</issn><issn>1559-131X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcFq3DAQhkVJSdI0D9BLETnkplZjrTT2MYQmLQT20kJuQpblXQVb2kp2kiYvX5ldCBR6khh9882In5BPwL8A5_g1Q8VFxTivWQNcsvodOQUpGwYC7o_KXUhkXCp-Qj7k_MB5BbJqjskJ1I1Ajs0peb1K2QVv6ZR8fPadYz50s3Ud3aT4NG2pScnlicaebufRBLp1OzNF64ZhHkyi1iTrQxwNXUqZ-vAYh0cfNvRmfb8WhrrnXRFkHwM1oaNDtGbwL2YqhY_kfW-G7M4P5xn5dfPt5_V3dre-_XF9dcfsSsiJSeva1qmukRJ7rEFao1SPQjWuQgGdUNC26HpQK2wNoGiEbFcAqkLbI6_FGbnce3cp_p7Lb_To87KuCS7OWSuspFIIBbz4B3yIcwplN12jlAIAFxvsIZtizsn1epf8aNIfDVwvseh9LLrEopdY9NLz-SCe29F1bx2HHApQ7YFcnsLGpbfJ_7f-BS6umZY</recordid><startdate>20090601</startdate><enddate>20090601</enddate><creator>Fei, Min</creator><creator>Lu, Mudan</creator><creator>Wang, You</creator><creator>Zhao, Yueming</creator><creator>He, Song</creator><creator>Gao, Shangfeng</creator><creator>Ke, Qing</creator><creator>Liu, Yonghua</creator><creator>Li, Peng</creator><creator>Cui, Xiaopeng</creator><creator>Shen, Aiguo</creator><creator>Cheng, Chun</creator><general>Humana Press Inc</general><general>Springer Nature B.V</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20090601</creationdate><title>Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization</title><author>Fei, Min ; Lu, Mudan ; Wang, You ; Zhao, Yueming ; He, Song ; Gao, Shangfeng ; Ke, Qing ; Liu, Yonghua ; Li, Peng ; Cui, Xiaopeng ; Shen, Aiguo ; Cheng, Chun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-5cebbe6d9557f7815ca66f7369e2731d361bb7ef1647ba173935b411627cf7083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Androstadienes - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Arsenicals - therapeutic use</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - enzymology</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Forkhead Box Protein O3</topic><topic>Forkhead Transcription Factors - analysis</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Hematology</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - enzymology</topic><topic>Liver Neoplasms - metabolism</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Networks and Pathways - drug effects</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Oxides - therapeutic use</topic><topic>Pathology</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fei, Min</creatorcontrib><creatorcontrib>Lu, Mudan</creatorcontrib><creatorcontrib>Wang, You</creatorcontrib><creatorcontrib>Zhao, Yueming</creatorcontrib><creatorcontrib>He, Song</creatorcontrib><creatorcontrib>Gao, Shangfeng</creatorcontrib><creatorcontrib>Ke, Qing</creatorcontrib><creatorcontrib>Liu, Yonghua</creatorcontrib><creatorcontrib>Li, Peng</creatorcontrib><creatorcontrib>Cui, Xiaopeng</creatorcontrib><creatorcontrib>Shen, Aiguo</creatorcontrib><creatorcontrib>Cheng, Chun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Medical oncology (Northwood, London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fei, Min</au><au>Lu, Mudan</au><au>Wang, You</au><au>Zhao, Yueming</au><au>He, Song</au><au>Gao, Shangfeng</au><au>Ke, Qing</au><au>Liu, Yonghua</au><au>Li, Peng</au><au>Cui, Xiaopeng</au><au>Shen, Aiguo</au><au>Cheng, Chun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization</atitle><jtitle>Medical oncology (Northwood, London, England)</jtitle><stitle>Med Oncol</stitle><addtitle>Med Oncol</addtitle><date>2009-06-01</date><risdate>2009</risdate><volume>26</volume><issue>2</issue><spage>178</spage><epage>185</epage><pages>178-185</pages><issn>1357-0560</issn><eissn>1559-131X</eissn><coden>MONCEZ</coden><abstract>Human hepatocellular carcinoma (HCC) remains incurable with current therapies, and novel biologically based therapies are urgently needed. Arsenic agents have long been used as anticancer agents in traditional Chinese medicine. In this study, to evaluate the effect of As
2
O
3
on HCC cells, we investigate cell growth inhibition, cell cycle arrest, and the molecular mechanism after As
2
O
3
treatment in human HCC cells in vitro. We detected the proliferation of HCC cells by the Cell Counting Kit and FACS/Calibur Flow Cytometer and analyzed the expression and localization of FOXO3a by Western blotting Analysis and Cell Fractionation. Furthermore, we study the Akt activation after As
2
O
3
treatment and the HCC cells proliferation after combination of As
2
O
3
with PI3K inhibitor Wortmannin. As
2
O
3
significantly inhibited the proliferation of all the three HCC cell lines (SMMC7721, HepG2, Hep3B) tested in this study in a dose-dependent manner. Western blotting revealed that treatment HCC cells HepG2 with As
2
O
3
resulted in the increasing of FOXO3a expression and triggered phosphorylation of FOXO3a at the Thr
32
residue decrease. This FOXO3a accumulation correlated well with the As
2
O
3
-induced reduction of active Akt. Nuclear and cytoplasmic protein extracts isolated from the HCC cell line HepG2 revealed that the amount of nuclear FOXO3a was increased by treatment with As
2
O
3
, whereas the amount of cytoplasmic FOXO3a was decreased. Both As
2
O
3
and PI3K/Akt inhibitor Wortmannin induced cell cycle arrest. However, compared with As
2
O
3
alone, PI3K inhibitor Wortmannin combined with As
2
O
3
enhanced the antitumor effect of As
2
O
3
through induction of apoptosis. These findings suggest that As
2
O
3
at a clinically safe concentration may be an effective chemotherapeutic agent, and that As
2
O
3
and PI3K/Akt inhibitor Wortmannin may synergize for HCC cells. Taken together, the present study may suggest a specific molecular mechanism by which HCC cell lines are susceptible to the As
2
O
3
therapy through FOXO3a expression and localization.</abstract><cop>New York</cop><pub>Humana Press Inc</pub><pmid>18937079</pmid><doi>10.1007/s12032-008-9105-8</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1357-0560 |
| ispartof | Medical oncology (Northwood, London, England), 2009-06, Vol.26 (2), p.178-185 |
| issn | 1357-0560 1559-131X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67256671 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Androstadienes - pharmacology Antineoplastic Agents - therapeutic use Arsenicals - therapeutic use Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Forkhead Box Protein O3 Forkhead Transcription Factors - analysis Forkhead Transcription Factors - metabolism Hematology Humans Internal Medicine Liver Neoplasms - drug therapy Liver Neoplasms - enzymology Liver Neoplasms - metabolism Medicine Medicine & Public Health Metabolic Networks and Pathways - drug effects Oncology Original Paper Oxides - therapeutic use Pathology Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-akt - metabolism |
| title | Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization |
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