| Title |
Cytotoxic effects of high concentrations of sodium ascorbate on human myeloid cell lines
|
|---|---|
| Published in |
Annals of Hematology, August 2015
|
| DOI | 10.1007/s00277-015-2464-2 |
| Pubmed ID | |
| Authors |
Domenico Mastrangelo, Lauretta Massai, Francesco Lo Coco, Nélida Inés Noguera, Loredana Borgia, Giuseppe Fioritoni, Anna Berardi, Antonio Iacone, Michela Muscettola, Elvira Pelosi, Germana Castelli, Ugo Testa, Francesco Di Pisa, Giovanni Grasso |
| Abstract |
The effect of high doses of intravenous (sodium) ascorbate (ASC) in the treatment of cancer has been controversial although there is growing evidence that ASC in high (pharmacologic) concentrations induces dose-dependent pro-apoptotic death of tumor cells, in vitro. Very few data are available on the role of ASC in the treatment of acute myeloid leukemia (AML). Ascorbate behaves as an antioxidant at low (physiologic), and as pro-oxidant at pharmacologic, concentrations, and this may account for the differences reported in different experimental settings, when human myeloid cell lines, such as HL60, were treated with ASC. Considering the myeloid origin of HL60 cells, and previous literature reports showing that some cell lines belonging to the myeloid lineage could be sensitive to the pro-apoptotic effects of high concentrations of ASC, we investigated in more details the effects of high doses (0.5 to 7 mM) of ASC in vitro, on a variety of human myeloid cell lines including the following: HL60, U937, NB4, NB4-R4 (retinoic acid [RA]-resistant), NB4/AsR (ATO-resistant) acute promyelocytic leukemia (APL)-derived cell lines, and K562 as well as on normal CD34+ progenitors derived from human cord blood. Our results indicate that all analyzed cell lines including all-trans retinoic acid (ATRA)- and arsenic trioxide (ATO)-resistant ones are highly sensitive to the cytotoxic, pro-oxidant effects of high doses of ASC, with an average 50 % lethal concentration (LC50) of 3 mM, depending on cell type, ASC concentration, and time of exposure. Conversely, high doses of ASC neither did exert significant cytotoxic effects nor impaired the differentiation potential in cord blood (CB) CD34+ normal cells. Since plasma ASC concentrations within the millimolar (mM) range can be easily and safely reached by intravenous administration, we conclude that phase I/II clinical trials using high doses of ASC should be designed for patients with advanced/refractory AML and APL. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 1 | 3% |
| Unknown | 39 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 23% |
| Researcher | 6 | 15% |
| Student > Ph. D. Student | 5 | 13% |
| Professor | 3 | 8% |
| Student > Master | 3 | 8% |
| Other | 5 | 13% |
| Unknown | 9 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 9 | 23% |
| Biochemistry, Genetics and Molecular Biology | 5 | 13% |
| Medicine and Dentistry | 4 | 10% |
| Chemistry | 2 | 5% |
| Psychology | 2 | 5% |
| Other | 5 | 13% |
| Unknown | 13 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 December 2015.
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#20,298,249
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Outputs from Annals of Hematology
#1,706
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#221,573
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Outputs of similar age from Annals of Hematology
#17
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