title: Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States; Institute of Cancer Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States; East China University of Science and Technology, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Central Microscopy Research Facility, University of Iowa, Iowa City, IA, United States.
authors.forename: Chantal
authors.initials: C
authors.lastname: Allamargot
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Coleman
authors.affiliation: Central Microscopy Research Facility, University of Iowa, Iowa City, IA, United States.
authors.forename: Randy
authors.initials: R
authors.lastname: Nessler
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States.
authors.forename: Ivana
authors.initials: I
authors.lastname: Frech
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States. Electronic address: guido-tricot@uiowa.edu.
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States. Electronic address: fenghuang-zhan@uiowa.edu.
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D004359:Drug Therapy, Combination; D006801:Humans; D007501:Iron / Q000737:chemistry; D008558:Melphalan / Q000627:therapeutic use; D051379:Mice; D016688:Mice, Inbred NOD; D008840:Microfilament Proteins; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D053668:Syndecan-1 / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: C112986:AIF1 protein, human; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D017382:Reactive Oxygen Species; D053668:Syndecan-1; D007501:Iron; D001205:Ascorbic Acid; D008558:Melphalan
keywords: Apoptosis-inducing factor 1; Multiple myeloma; Pharmacologically-dosed ascorbic acid