Cited by 109Multiple Myeloma Research and TreatmentsVitamin C and Antioxidants ResearchUbiquitin and proteasome pathways

Ascorbic acid inhibits antitumor activity of bortezomib in vivo

Perrone, G, Hideshima, T, Ikeda, H, Okawa, Y, Calabrese, E, Gorgun, G, Santo, L, Cirstea, D +5 more·2009·Leukemia

Abstract

Earlier studies have shown that ascorbic acid (vitamin C) inhibits bortezomib-induced cytotoxicity against cancer cells in vitro. However, the clinical significance of vitamin C on bortezomib treatment is unclear. In this study, we examined whether daily oral intake of vitamin C inhibits antimultiple myeloma (MM) activities of bortezomib. Vitamin C, at orally achievable concentrations, inhibited in vitro MM cell cytotoxicity of bortezomib and blocked its inhibitory effect on 20S proteasome activity. Specifically, plasma collected from healthy volunteers taking 1 g/day vitamin C reduced bortezomib-induced MM cell death in vitro. This antagonistic effect of vitamin C against proteasome inhibitors is limited to the boronate class of inhibitors (bortezomib and MG262). In vivo activity of this combination treatment was then evaluated using our xenograft model of human MM in SCID (severe combined immune-deficient) mice. Bortezomib (0.1 mg/kg twice a week for 4 weeks) significantly inhibits in vivo MM cell growth, which was blocked by oral vitamin C (40 mg/kg/day). Therefore, our results for the first time show that vitamin C can significantly reduce the activity of bortezomib treatment in vivo; and importantly, suggest that patients receiving treatment with bortezomib should avoid taking vitamin C dietary supplements.

Integrity signals

Registry

Crossref · 10.1038/leu.2009.83

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Perrone, G., Hideshima, T., Ikeda, H., Okawa, Y., Calabrese, E., Gorgun, G., Santo, L., Cirstea, D., Raje, N., Chauhan, D., Baccarani, M., Cavo, M., & Anderson, K. C.
Affiliations
  • Harvard University (US)
  • University of Bologna (IT)
Corresponding author
Anderson, K C
Venue
Leukemia
Published
2009-04-16
Volume
23
Issue
9
Pages
1679-1686
ISSN
  • 0887-6924 (ISSN-L)
  • 1476-5551
OpenAlex
W2064451393
Cited by
109
References
37
Citations by year
2026: 4 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 3 · 2014: 9 · 2013: 7 · 2012: 7
FWCI
7.67
Type
journal article
Language
en
Open access
closed
Locations
  • Leukemia (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
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 › Ubiquitin and proteasome pathways
Keywords
vitamin C, bortezomib, multiple myeloma, proteasome inhibitors, 20S proteasome, drug interactions, xenograft models, dietary supplements, combination therapy
MeSH terms
Bortezomib, Animals, Antineoplastic Agents, Antioxidants, Ascorbic Acid, Boronic Acids, Humans, Multiple Myeloma, Pyrazines, Cell Line, Tumor, Cell Proliferation, Mice, Proteasome Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review