Related Experiment Video
Updated: Mar 7, 2026
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid
Jiliang Xia1, Hongwei Xu2, Xiaoyan Zhang3
1Department 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.
Pharmacologically-dosed ascorbic acid (PAA) with iron generates reactive oxygen species (ROS) to selectively kill multiple myeloma (MM) tumor cells. This novel approach shows promise for treating MM with reduced toxicity.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- High-dose chemotherapy for multiple myeloma (MM) poses significant toxicity risks to normal cells.
- There is a critical need for therapeutic strategies that selectively target MM tumor cells or reduce standard drug dosages without compromising efficacy.
Purpose of the Study:
- To investigate the efficacy of pharmacologically-dosed ascorbic acid (PAA) in combination with iron as a targeted therapy for multiple myeloma.
- To evaluate the selective killing of CD138+ MM tumor cells by PAA and its effects on tumor formation in vivo.
Main Methods:
- Treatment of multiple myeloma (MM) and related cells with pharmacologically-dosed ascorbic acid (PAA) in the presence of iron.
- Assessment of reactive oxygen species (ROS) generation and subsequent cell death induction.
- In vitro testing on primary cancer cells and cell lines, and in vivo studies using MM xenograft mouse models.
Main Results:
- PAA with iron induced the formation of reactive oxygen species (ROS), leading to selective cell death in CD138+ MM tumor cells from MM and smoldering MM (SMM) patients.
- PAA did not induce cell death in cells from monoclonal gammopathy undetermined significance (MGUS) patients.
- PAA, alone or combined with melphalan, demonstrated inhibition of tumor formation in MM xenograft mice.
Conclusions:
- Pharmacologically-dosed ascorbic acid (PAA) in the presence of iron is a potent agent for selectively targeting and killing multiple myeloma tumor cells.
- PAA exhibits therapeutic potential as a standalone treatment or in combination with conventional chemotherapy, offering a promising strategy to reduce toxicity in MM treatment.
