Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
Open accessAbstract
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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Multiple myeloma cells have a larger labile iron pool because they express little ferroportin 1, and this made them selectively sensitive to pharmacological ascorbate.
“multiple myeloma cells have an elevated labile iron pool owing to the low expression of the iron exporter, ferroportin 1, which led to their selective sensitivity to pharmacological doses of ascorbate44.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [44]
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- Authors
- Xia, J., Xu, H., Zhang, X., Allamargot, C., Coleman, K. L., Nessler, R., Frech, I., Tricot, G., & Zhan, F.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Tricot, Guido
- Zhan, Fenghuang
- Venue
- EBioMedicine
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 18
- Pages
- 41-49
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC5405162
- OpenAlex
- W2588241479
- Cited by
- 63
- References
- 78
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 7 · 2022: 15 · 2021: 6 · 2020: 11 · 2019: 3 · 2018: 5 · 2017: 3
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EBioMedicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- multiple myeloma, vitamin C, iron, reactive oxygen species, oxidative cell death, selective tumor cell killing, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, melphalan, combination therapy, xenograft tumor growth
- MeSH terms
- Animals, Antineoplastic Agents, Ascorbic Acid, Calcium-Binding Proteins, DNA-Binding Proteins, Drug Therapy, Combination, Humans, Iron, Melphalan, Microfilament Proteins, Multiple Myeloma, Transplantation, Heterologous, Mice, Inbred NOD, Apoptosis, Reactive Oxygen Species, Cell Line, Tumor, Mice, Syndecan-1
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