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Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iro...

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Autores principales: Xia, Jiliang, Xu, Hongwei, Zhang, Xiaoyan, Allamargot, Chantal, Coleman, Kristen L., Nessler, Randy, Frech, Ivana, Tricot, Guido, Zhan, Fenghuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405162/
https://www.ncbi.nlm.nih.gov/pubmed/28229908
http://dx.doi.org/10.1016/j.ebiom.2017.02.011
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author Xia, Jiliang
Xu, Hongwei
Zhang, Xiaoyan
Allamargot, Chantal
Coleman, Kristen L.
Nessler, Randy
Frech, Ivana
Tricot, Guido
Zhan, Fenghuang
author_facet Xia, Jiliang
Xu, Hongwei
Zhang, Xiaoyan
Allamargot, Chantal
Coleman, Kristen L.
Nessler, Randy
Frech, Ivana
Tricot, Guido
Zhan, Fenghuang
author_sort Xia, Jiliang
collection PubMed
description High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138(+) MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients. PAA alone or in combination with melphalan inhibits tumor formation in MM xenograft mice. This study shows PAA efficacy on primary cancer cells and cell lines in vitro and in vivo.
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spelling pubmed-54051622017-05-05 Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid Xia, Jiliang Xu, Hongwei Zhang, Xiaoyan Allamargot, Chantal Coleman, Kristen L. Nessler, Randy Frech, Ivana Tricot, Guido Zhan, Fenghuang EBioMedicine Research Paper High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138(+) MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients. PAA alone or in combination with melphalan inhibits tumor formation in MM xenograft mice. This study shows PAA efficacy on primary cancer cells and cell lines in vitro and in vivo. Elsevier 2017-02-16 /pmc/articles/PMC5405162/ /pubmed/28229908 http://dx.doi.org/10.1016/j.ebiom.2017.02.011 Text en © 2017 The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Xia, Jiliang
Xu, Hongwei
Zhang, Xiaoyan
Allamargot, Chantal
Coleman, Kristen L.
Nessler, Randy
Frech, Ivana
Tricot, Guido
Zhan, Fenghuang
Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
title Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
title_full Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
title_fullStr Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
title_full_unstemmed Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
title_short Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
title_sort multiple myeloma tumor cells are selectively killed by pharmacologically-dosed ascorbic acid
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405162/
https://www.ncbi.nlm.nih.gov/pubmed/28229908
http://dx.doi.org/10.1016/j.ebiom.2017.02.011
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