Ascorbic acid inhibits antitumor activity of bortezomib in vivo
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.
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- 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
- ORCID
- 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
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