The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in vitro and in vivo study
Objective To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo. Methods Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A gli...
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| Veröffentlicht in: | Journal of international medical research 2013-02, Vol.41 (1), p.72-81 |
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| creator | Wang, Haifeng Zhang, Shuyan Zhong, Jiateng Zhang, Jizhou Luo, Yinan Ge, Pengfei |
| description | Objective
To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo.
Methods
Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A glioma xenograft model was established in mice and animals were treated with 0, 1 or 5 µg/20 g body weight lactacystin for 7 days. Animals were sacrificed on day 17 after completion of treatment. Apoptosis in tumour tissue was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of B cell lymphoma 2 (Bcl-2), and Bcl2-associated X protein (Bax) protein and mRNA, were determined in C6 cells and tumour tissues.
Results
Lactacystin significantly inhibited the proliferation of C6 cells, increased apoptosis and reduced mitochondrial membrane potential in vitro, and suppressed tumour growth in vivo. Lactacystin increased the ratio of Bax to Bcl-2 at the mRNA and protein levels, both in vitro and in vivo.
Conclusions
The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma. |
| doi_str_mv | 10.1177/0300060513476992 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_AFRWT</sourceid><recordid>TN_cdi_proquest_miscellaneous_1325332579</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0300060513476992</sage_id><sourcerecordid>1325332579</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-289a1909ccec0d07f3b26d29865c7939cff8029df4813b9c8a9f8124d5baf9423</originalsourceid><addsrcrecordid>eNp1kE2LFDEQhoMo7uzo3ZPkInhpzUd_xduy6CoseFnPTXW6spOlu9Om0oMD_hh_i7_MDDMqCB6KkKqn3pCHsRdSvJGyad4KLYSoRSV12dTGqEdsI8tGFyr3H7PNcVwc5xfskuhBiFLVlXrKLpSuaiO12rDvdzvkSwwJgcKE3M873_sUIh_BJrAHSn7m-A1jIu5zpR1GWHBN3nJ0Dm3uhZnfjz5MwPceOCxhSYE8veNXcw78-WPvUwwc5uF82wdOaR0Oz9gTByPh8_O5ZV8-vL-7_ljcfr75dH11W9hSmFSo1oA0wliLVgyicbpX9aBMW1e2MdpY51qhzODKVure2BaMa6Uqh6oHZ0qlt-z1KTd_9OuKlLrJk8VxhBnDSl02UelcOWzLxAm1MRBFdN0S_QTx0EnRHZ13_zrPKy_P6Ws_4fBn4bfkDLw6A0AWRhdhtp7-ck3V6qY6csWJI7jH7iGscc5W_v_wL3vJmQM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1325332579</pqid></control><display><type>article</type><title>The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in vitro and in vivo study</title><source>Sage Journals GOLD Open Access 2024</source><creator>Wang, Haifeng ; Zhang, Shuyan ; Zhong, Jiateng ; Zhang, Jizhou ; Luo, Yinan ; Ge, Pengfei</creator><creatorcontrib>Wang, Haifeng ; Zhang, Shuyan ; Zhong, Jiateng ; Zhang, Jizhou ; Luo, Yinan ; Ge, Pengfei</creatorcontrib><description>Objective
To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo.
Methods
Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A glioma xenograft model was established in mice and animals were treated with 0, 1 or 5 µg/20 g body weight lactacystin for 7 days. Animals were sacrificed on day 17 after completion of treatment. Apoptosis in tumour tissue was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of B cell lymphoma 2 (Bcl-2), and Bcl2-associated X protein (Bax) protein and mRNA, were determined in C6 cells and tumour tissues.
Results
Lactacystin significantly inhibited the proliferation of C6 cells, increased apoptosis and reduced mitochondrial membrane potential in vitro, and suppressed tumour growth in vivo. Lactacystin increased the ratio of Bax to Bcl-2 at the mRNA and protein levels, both in vitro and in vivo.
Conclusions
The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma.</description><identifier>ISSN: 0300-0605</identifier><identifier>EISSN: 1473-2300</identifier><identifier>DOI: 10.1177/0300060513476992</identifier><identifier>PMID: 23569132</identifier><identifier>CODEN: JIMRBV</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Acetylcysteine - analogs & derivatives ; Acetylcysteine - pharmacology ; Acetylcysteine - therapeutic use ; Animals ; Apoptosis - drug effects ; Apoptosis - genetics ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Biological and medical sciences ; Brain Neoplasms - drug therapy ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Cell Line, Tumor ; Cell Survival - drug effects ; Gene Expression Regulation, Neoplastic - drug effects ; General pharmacology ; Glioma - drug therapy ; Glioma - genetics ; Glioma - pathology ; Medical sciences ; Membrane Potential, Mitochondrial - drug effects ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neurology ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Proteasome Inhibitors - pharmacology ; Proteasome Inhibitors - therapeutic use ; Rats ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Tumor Burden - drug effects ; Tumors of the nervous system. Phacomatoses ; Xenograft Model Antitumor Assays</subject><ispartof>Journal of international medical research, 2013-02, Vol.41 (1), p.72-81</ispartof><rights>The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-289a1909ccec0d07f3b26d29865c7939cff8029df4813b9c8a9f8124d5baf9423</citedby><cites>FETCH-LOGICAL-c409t-289a1909ccec0d07f3b26d29865c7939cff8029df4813b9c8a9f8124d5baf9423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0300060513476992$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0300060513476992$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,860,21946,27832,27903,27904,44924,45312</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0300060513476992?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27583752$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23569132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Haifeng</creatorcontrib><creatorcontrib>Zhang, Shuyan</creatorcontrib><creatorcontrib>Zhong, Jiateng</creatorcontrib><creatorcontrib>Zhang, Jizhou</creatorcontrib><creatorcontrib>Luo, Yinan</creatorcontrib><creatorcontrib>Ge, Pengfei</creatorcontrib><title>The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in vitro and in vivo study</title><title>Journal of international medical research</title><addtitle>International Medical Research</addtitle><description>Objective
To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo.
Methods
Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A glioma xenograft model was established in mice and animals were treated with 0, 1 or 5 µg/20 g body weight lactacystin for 7 days. Animals were sacrificed on day 17 after completion of treatment. Apoptosis in tumour tissue was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of B cell lymphoma 2 (Bcl-2), and Bcl2-associated X protein (Bax) protein and mRNA, were determined in C6 cells and tumour tissues.
Results
Lactacystin significantly inhibited the proliferation of C6 cells, increased apoptosis and reduced mitochondrial membrane potential in vitro, and suppressed tumour growth in vivo. Lactacystin increased the ratio of Bax to Bcl-2 at the mRNA and protein levels, both in vitro and in vivo.
Conclusions
The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma.</description><subject>Acetylcysteine - analogs & derivatives</subject><subject>Acetylcysteine - pharmacology</subject><subject>Acetylcysteine - therapeutic use</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>General pharmacology</subject><subject>Glioma - drug therapy</subject><subject>Glioma - genetics</subject><subject>Glioma - pathology</subject><subject>Medical sciences</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neurology</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Proteasome Inhibitors - pharmacology</subject><subject>Proteasome Inhibitors - therapeutic use</subject><subject>Rats</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Tumor Burden - drug effects</subject><subject>Tumors of the nervous system. Phacomatoses</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0300-0605</issn><issn>1473-2300</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE2LFDEQhoMo7uzo3ZPkInhpzUd_xduy6CoseFnPTXW6spOlu9Om0oMD_hh_i7_MDDMqCB6KkKqn3pCHsRdSvJGyad4KLYSoRSV12dTGqEdsI8tGFyr3H7PNcVwc5xfskuhBiFLVlXrKLpSuaiO12rDvdzvkSwwJgcKE3M873_sUIh_BJrAHSn7m-A1jIu5zpR1GWHBN3nJ0Dm3uhZnfjz5MwPceOCxhSYE8veNXcw78-WPvUwwc5uF82wdOaR0Oz9gTByPh8_O5ZV8-vL-7_ljcfr75dH11W9hSmFSo1oA0wliLVgyicbpX9aBMW1e2MdpY51qhzODKVure2BaMa6Uqh6oHZ0qlt-z1KTd_9OuKlLrJk8VxhBnDSl02UelcOWzLxAm1MRBFdN0S_QTx0EnRHZ13_zrPKy_P6Ws_4fBn4bfkDLw6A0AWRhdhtp7-ck3V6qY6csWJI7jH7iGscc5W_v_wL3vJmQM</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Wang, Haifeng</creator><creator>Zhang, Shuyan</creator><creator>Zhong, Jiateng</creator><creator>Zhang, Jizhou</creator><creator>Luo, Yinan</creator><creator>Ge, Pengfei</creator><general>SAGE Publications</general><general>Sage Publications</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>20130201</creationdate><title>The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in vitro and in vivo study</title><author>Wang, Haifeng ; Zhang, Shuyan ; Zhong, Jiateng ; Zhang, Jizhou ; Luo, Yinan ; Ge, Pengfei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-289a1909ccec0d07f3b26d29865c7939cff8029df4813b9c8a9f8124d5baf9423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetylcysteine - analogs & derivatives</topic><topic>Acetylcysteine - pharmacology</topic><topic>Acetylcysteine - therapeutic use</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biological and medical sciences</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>General pharmacology</topic><topic>Glioma - drug therapy</topic><topic>Glioma - genetics</topic><topic>Glioma - pathology</topic><topic>Medical sciences</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neurology</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Proteasome Inhibitors - pharmacology</topic><topic>Proteasome Inhibitors - therapeutic use</topic><topic>Rats</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Tumor Burden - drug effects</topic><topic>Tumors of the nervous system. Phacomatoses</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Haifeng</creatorcontrib><creatorcontrib>Zhang, Shuyan</creatorcontrib><creatorcontrib>Zhong, Jiateng</creatorcontrib><creatorcontrib>Zhang, Jizhou</creatorcontrib><creatorcontrib>Luo, Yinan</creatorcontrib><creatorcontrib>Ge, Pengfei</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of international medical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Wang, Haifeng</au><au>Zhang, Shuyan</au><au>Zhong, Jiateng</au><au>Zhang, Jizhou</au><au>Luo, Yinan</au><au>Ge, Pengfei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in vitro and in vivo study</atitle><jtitle>Journal of international medical research</jtitle><addtitle>International Medical Research</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>41</volume><issue>1</issue><spage>72</spage><epage>81</epage><pages>72-81</pages><issn>0300-0605</issn><eissn>1473-2300</eissn><coden>JIMRBV</coden><abstract>Objective
To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo.
Methods
Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A glioma xenograft model was established in mice and animals were treated with 0, 1 or 5 µg/20 g body weight lactacystin for 7 days. Animals were sacrificed on day 17 after completion of treatment. Apoptosis in tumour tissue was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of B cell lymphoma 2 (Bcl-2), and Bcl2-associated X protein (Bax) protein and mRNA, were determined in C6 cells and tumour tissues.
Results
Lactacystin significantly inhibited the proliferation of C6 cells, increased apoptosis and reduced mitochondrial membrane potential in vitro, and suppressed tumour growth in vivo. Lactacystin increased the ratio of Bax to Bcl-2 at the mRNA and protein levels, both in vitro and in vivo.
Conclusions
The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>23569132</pmid><doi>10.1177/0300060513476992</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Sage Journals GOLD Open Access 2024 |
| subjects | Acetylcysteine - analogs & derivatives Acetylcysteine - pharmacology Acetylcysteine - therapeutic use Animals Apoptosis - drug effects Apoptosis - genetics bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Biological and medical sciences Brain Neoplasms - drug therapy Brain Neoplasms - genetics Brain Neoplasms - pathology Cell Line, Tumor Cell Survival - drug effects Gene Expression Regulation, Neoplastic - drug effects General pharmacology Glioma - drug therapy Glioma - genetics Glioma - pathology Medical sciences Membrane Potential, Mitochondrial - drug effects Mice Mice, Inbred BALB C Mice, Nude Neurology Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Proteasome Inhibitors - pharmacology Proteasome Inhibitors - therapeutic use Rats RNA, Messenger - genetics RNA, Messenger - metabolism Tumor Burden - drug effects Tumors of the nervous system. Phacomatoses Xenograft Model Antitumor Assays |
| title | The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in vitro and in vivo study |
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