Ascorbic acid inhibits antitumor activity of bortezomib in vivo
Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells in vitro . However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultip...
Gespeichert in:
| Veröffentlicht in: | Leukemia 2009-09, Vol.23 (9), p.1679-1686 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1686 |
|---|---|
| container_issue | 9 |
| container_start_page | 1679 |
| container_title | Leukemia |
| container_volume | 23 |
| creator | Perrone, G Hideshima, T Ikeda, H Okawa, Y Calabrese, E Gorgun, G Santo, L Cirstea, D Raje, N Chauhan, D Baccarani, M Cavo, M Anderson, K C |
| description | Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells
in vitro
. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited
in vitro
MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death
in vitro
. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262).
In vivo
activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits
in vivo
MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day). Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment
in vivo
; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements. |
| doi_str_mv | 10.1038/leu.2009.83 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_67638857</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A209638973</galeid><sourcerecordid>A209638973</sourcerecordid><originalsourceid>FETCH-LOGICAL-c604t-a1ccd8d325e15ec3058741518de1f068613d0b7891c842d0a16f78be7b21b23b3</originalsourceid><addsrcrecordid>eNqFkk2LFDEQhoMo7uzqybs0yu5Fe0wl3fk4ybD4BQte9BySdHonS3dnTdID6683zQyOKyuSQ6DqqXqrihehF4DXgKl4N7h5TTCWa0EfoRU0nNVt28JjtMJC8JpJ0pyg05RuMF6S7Ck6AUmZlIyu0PtNsiEabyttfVf5aeuNz6nSU_Z5HkMs8ex3Pt9Voa9MiNn9DKM3hax2fheeoSe9HpJ7fvjP0PePH75dfq6vvn76crm5qi3DTa41WNuJjpLWQessxa3gDbQgOgc9ZoIB7bDhQoIVDemwBtZzYRw3BAyhhp6hi33f2xh-zC5lNfpk3TDoyYU5KcYZFaLl_wUJllRwgAK-_gu8CXOcyhKKsKblRHKghXr1T4rgoocbcmx1rQen_NSHHLVddNWm6JXJJF9arR-gyuvc6G2YXO9L_F7BxR8FW6eHvE1hmLMPU7oPvtmDNoaUouvVbfSjjncKsFo8oopH1OIRJRb65WGl2YyuO7IHUxTg_ADoZPXQRz1Zn35zBCSRhC-nfrvnUklN1y4eb_OQ7i-uWc3u</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>220573042</pqid></control><display><type>article</type><title>Ascorbic acid inhibits antitumor activity of bortezomib in vivo</title><source>MEDLINE</source><source>Springer Journals</source><source>Nature</source><source>EZB Electronic Journals Library</source><creator>Perrone, G ; Hideshima, T ; Ikeda, H ; Okawa, Y ; Calabrese, E ; Gorgun, G ; Santo, L ; Cirstea, D ; Raje, N ; Chauhan, D ; Baccarani, M ; Cavo, M ; Anderson, K C</creator><creatorcontrib>Perrone, G ; Hideshima, T ; Ikeda, H ; Okawa, Y ; Calabrese, E ; Gorgun, G ; Santo, L ; Cirstea, D ; Raje, N ; Chauhan, D ; Baccarani, M ; Cavo, M ; Anderson, K C</creatorcontrib><description>Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells
in vitro
. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited
in vitro
MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death
in vitro
. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262).
In vivo
activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits
in vivo
MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day). Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment
in vivo
; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2009.83</identifier><identifier>PMID: 19369963</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Acids ; Animals ; Anticancer properties ; Antineoplastic Agents - antagonists & inhibitors ; Antioxidants - pharmacology ; Antitumor activity ; Ascorbic acid ; Ascorbic Acid - pharmacology ; Biocompatibility ; Biological and medical sciences ; Boronic Acids - antagonists & inhibitors ; Bortezomib ; Cancer ; Cancer cells ; Cancer Research ; Cell death ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Critical Care Medicine ; Cytotoxicity ; Diet ; Dietary supplements ; Dosage and administration ; FDA approval ; Health aspects ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Immunodeficiencies. Immunoglobulinopathies ; Immunoglobulinopathies ; Immunopathology ; In vivo methods and tests ; Inhibitor drugs ; Inhibitors ; Intensive ; Internal Medicine ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Multiple myeloma ; Multiple Myeloma - drug therapy ; Myeloma ; Oncology ; original-article ; Physiological aspects ; Plasma ; Proteasome Inhibitors ; Pyrazines - antagonists & inhibitors ; Severe combined immunodeficiency ; Targeted cancer therapy ; Toxicity ; Vitamin C ; Xenografts ; Xenotransplantation</subject><ispartof>Leukemia, 2009-09, Vol.23 (9), p.1679-1686</ispartof><rights>Macmillan Publishers Limited 2009</rights><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2009</rights><rights>Macmillan Publishers Limited 2009.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c604t-a1ccd8d325e15ec3058741518de1f068613d0b7891c842d0a16f78be7b21b23b3</citedby><cites>FETCH-LOGICAL-c604t-a1ccd8d325e15ec3058741518de1f068613d0b7891c842d0a16f78be7b21b23b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2009.83$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2009.83$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21929277$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19369963$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perrone, G</creatorcontrib><creatorcontrib>Hideshima, T</creatorcontrib><creatorcontrib>Ikeda, H</creatorcontrib><creatorcontrib>Okawa, Y</creatorcontrib><creatorcontrib>Calabrese, E</creatorcontrib><creatorcontrib>Gorgun, G</creatorcontrib><creatorcontrib>Santo, L</creatorcontrib><creatorcontrib>Cirstea, D</creatorcontrib><creatorcontrib>Raje, N</creatorcontrib><creatorcontrib>Chauhan, D</creatorcontrib><creatorcontrib>Baccarani, M</creatorcontrib><creatorcontrib>Cavo, M</creatorcontrib><creatorcontrib>Anderson, K C</creatorcontrib><title>Ascorbic acid inhibits antitumor activity of bortezomib in vivo</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells
in vitro
. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited
in vitro
MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death
in vitro
. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262).
In vivo
activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits
in vivo
MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day). Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment
in vivo
; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements.</description><subject>Acids</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Antineoplastic Agents - antagonists & inhibitors</subject><subject>Antioxidants - pharmacology</subject><subject>Antitumor activity</subject><subject>Ascorbic acid</subject><subject>Ascorbic Acid - pharmacology</subject><subject>Biocompatibility</subject><subject>Biological and medical sciences</subject><subject>Boronic Acids - antagonists & inhibitors</subject><subject>Bortezomib</subject><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cancer Research</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Critical Care Medicine</subject><subject>Cytotoxicity</subject><subject>Diet</subject><subject>Dietary supplements</subject><subject>Dosage and administration</subject><subject>FDA approval</subject><subject>Health aspects</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>In vivo methods and tests</subject><subject>Inhibitor drugs</subject><subject>Inhibitors</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Myeloma</subject><subject>Oncology</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Proteasome Inhibitors</subject><subject>Pyrazines - antagonists & inhibitors</subject><subject>Severe combined immunodeficiency</subject><subject>Targeted cancer therapy</subject><subject>Toxicity</subject><subject>Vitamin C</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkk2LFDEQhoMo7uzqybs0yu5Fe0wl3fk4ybD4BQte9BySdHonS3dnTdID6683zQyOKyuSQ6DqqXqrihehF4DXgKl4N7h5TTCWa0EfoRU0nNVt28JjtMJC8JpJ0pyg05RuMF6S7Ck6AUmZlIyu0PtNsiEabyttfVf5aeuNz6nSU_Z5HkMs8ex3Pt9Voa9MiNn9DKM3hax2fheeoSe9HpJ7fvjP0PePH75dfq6vvn76crm5qi3DTa41WNuJjpLWQessxa3gDbQgOgc9ZoIB7bDhQoIVDemwBtZzYRw3BAyhhp6hi33f2xh-zC5lNfpk3TDoyYU5KcYZFaLl_wUJllRwgAK-_gu8CXOcyhKKsKblRHKghXr1T4rgoocbcmx1rQen_NSHHLVddNWm6JXJJF9arR-gyuvc6G2YXO9L_F7BxR8FW6eHvE1hmLMPU7oPvtmDNoaUouvVbfSjjncKsFo8oopH1OIRJRb65WGl2YyuO7IHUxTg_ADoZPXQRz1Zn35zBCSRhC-nfrvnUklN1y4eb_OQ7i-uWc3u</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Perrone, G</creator><creator>Hideshima, T</creator><creator>Ikeda, H</creator><creator>Okawa, Y</creator><creator>Calabrese, E</creator><creator>Gorgun, G</creator><creator>Santo, L</creator><creator>Cirstea, D</creator><creator>Raje, N</creator><creator>Chauhan, D</creator><creator>Baccarani, M</creator><creator>Cavo, M</creator><creator>Anderson, K C</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20090901</creationdate><title>Ascorbic acid inhibits antitumor activity of bortezomib in vivo</title><author>Perrone, G ; Hideshima, T ; Ikeda, H ; Okawa, Y ; Calabrese, E ; Gorgun, G ; Santo, L ; Cirstea, D ; Raje, N ; Chauhan, D ; Baccarani, M ; Cavo, M ; Anderson, K C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c604t-a1ccd8d325e15ec3058741518de1f068613d0b7891c842d0a16f78be7b21b23b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acids</topic><topic>Animals</topic><topic>Anticancer properties</topic><topic>Antineoplastic Agents - antagonists & inhibitors</topic><topic>Antioxidants - pharmacology</topic><topic>Antitumor activity</topic><topic>Ascorbic acid</topic><topic>Ascorbic Acid - pharmacology</topic><topic>Biocompatibility</topic><topic>Biological and medical sciences</topic><topic>Boronic Acids - antagonists & inhibitors</topic><topic>Bortezomib</topic><topic>Cancer</topic><topic>Cancer cells</topic><topic>Cancer Research</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Critical Care Medicine</topic><topic>Cytotoxicity</topic><topic>Diet</topic><topic>Dietary supplements</topic><topic>Dosage and administration</topic><topic>FDA approval</topic><topic>Health aspects</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>In vivo methods and tests</topic><topic>Inhibitor drugs</topic><topic>Inhibitors</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukemia</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Myeloma</topic><topic>Oncology</topic><topic>original-article</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Proteasome Inhibitors</topic><topic>Pyrazines - antagonists & inhibitors</topic><topic>Severe combined immunodeficiency</topic><topic>Targeted cancer therapy</topic><topic>Toxicity</topic><topic>Vitamin C</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perrone, G</creatorcontrib><creatorcontrib>Hideshima, T</creatorcontrib><creatorcontrib>Ikeda, H</creatorcontrib><creatorcontrib>Okawa, Y</creatorcontrib><creatorcontrib>Calabrese, E</creatorcontrib><creatorcontrib>Gorgun, G</creatorcontrib><creatorcontrib>Santo, L</creatorcontrib><creatorcontrib>Cirstea, D</creatorcontrib><creatorcontrib>Raje, N</creatorcontrib><creatorcontrib>Chauhan, D</creatorcontrib><creatorcontrib>Baccarani, M</creatorcontrib><creatorcontrib>Cavo, M</creatorcontrib><creatorcontrib>Anderson, K C</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>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perrone, G</au><au>Hideshima, T</au><au>Ikeda, H</au><au>Okawa, Y</au><au>Calabrese, E</au><au>Gorgun, G</au><au>Santo, L</au><au>Cirstea, D</au><au>Raje, N</au><au>Chauhan, D</au><au>Baccarani, M</au><au>Cavo, M</au><au>Anderson, K C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ascorbic acid inhibits antitumor activity of bortezomib in vivo</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>23</volume><issue>9</issue><spage>1679</spage><epage>1686</epage><pages>1679-1686</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells
in vitro
. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited
in vitro
MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death
in vitro
. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262).
In vivo
activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits
in vivo
MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day). Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment
in vivo
; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19369963</pmid><doi>10.1038/leu.2009.83</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2009-09, Vol.23 (9), p.1679-1686 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67638857 |
| source | MEDLINE; Springer Journals; Nature; EZB Electronic Journals Library |
| subjects | Acids Animals Anticancer properties Antineoplastic Agents - antagonists & inhibitors Antioxidants - pharmacology Antitumor activity Ascorbic acid Ascorbic Acid - pharmacology Biocompatibility Biological and medical sciences Boronic Acids - antagonists & inhibitors Bortezomib Cancer Cancer cells Cancer Research Cell death Cell Line, Tumor Cell Proliferation - drug effects Critical Care Medicine Cytotoxicity Diet Dietary supplements Dosage and administration FDA approval Health aspects Hematologic and hematopoietic diseases Hematology Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulinopathies Immunopathology In vivo methods and tests Inhibitor drugs Inhibitors Intensive Internal Medicine Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Medicine Medicine & Public Health Mice Multiple myeloma Multiple Myeloma - drug therapy Myeloma Oncology original-article Physiological aspects Plasma Proteasome Inhibitors Pyrazines - antagonists & inhibitors Severe combined immunodeficiency Targeted cancer therapy Toxicity Vitamin C Xenografts Xenotransplantation |
| title | Ascorbic acid inhibits antitumor activity of bortezomib in vivo |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T20%3A50%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ascorbic%20acid%20inhibits%20antitumor%20activity%20of%20bortezomib%20in%20vivo&rft.jtitle=Leukemia&rft.au=Perrone,%20G&rft.date=2009-09-01&rft.volume=23&rft.issue=9&rft.spage=1679&rft.epage=1686&rft.pages=1679-1686&rft.issn=0887-6924&rft.eissn=1476-5551&rft.coden=LEUKED&rft_id=info:doi/10.1038/leu.2009.83&rft_dat=%3Cgale_proqu%3EA209638973%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=220573042&rft_id=info:pmid/19369963&rft_galeid=A209638973&rfr_iscdi=true |