Ascorbic acid inhibits antitumor activity of bortezomib in vivo

G. Perrone, T. Hideshima, H. Ikeda, Y. Okawa, E. Calabrese, G. Gorgun, L. Santo, D. Cirstea, N. Raje, D. Chauhan, M. Baccarani, M. Cavo, K. C. Anderson

Research output: Contribution to journalArticle

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 bortezomibinduced 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.

Original languageEnglish
Pages (from-to)1679-1686
Number of pages8
JournalLeukemia
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 2009

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Keywords

  • Antioxidant
  • Ascorbic acid
  • Bortezomib
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine
  • Medicine(all)

Cite this

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. (2009). Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia, 23(9), 1679-1686. https://doi.org/10.1038/leu.2009.83