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EBioMedicine. 2017 Apr;18:41-49. doi: 10.1016/j.ebiom.2017.02.011. Epub 2017 Feb 16.

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

Author information

1
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.
2
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States.
3
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.
4
Central Microscopy Research Facility, University of Iowa, Iowa City, IA, United States.
5
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.
6
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.

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.

KEYWORDS:

Apoptosis-inducing factor 1; Multiple myeloma; Pharmacologically-dosed ascorbic acid

PMID:
28229908
PMCID:
PMC5405162
DOI:
10.1016/j.ebiom.2017.02.011
[Indexed for MEDLINE]
Free PMC Article

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