Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
Jiliang Xia,
Hongwei Xu,
Xiaoyan Zhang,
Chantal Allamargot,
Kristen L. Coleman,
Randy Nessler,
Ivana Frech,
Guido Tricot,
Fenghuang Zhan
Affiliations
Jiliang Xia
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
Hongwei Xu
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
Xiaoyan Zhang
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
Chantal Allamargot
Central Microscopy Research Facility, University of Iowa, Iowa City, IA, United States
Kristen L. Coleman
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
Randy Nessler
Central Microscopy Research Facility, University of Iowa, Iowa City, IA, United States
Ivana Frech
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
Guido Tricot
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
Fenghuang Zhan
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
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.
