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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3835-3846. Prepublished online as a Blood First Edition Paper on July 16, 2008; DOI 10.1182/blood-2008-04-150227. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-150227v1 112/9/3835    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, F.-T. Articles by Jia, L. Search for Related Content PubMed PubMed Citation Articles by Liu, F.-T. Articles by Jia, L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 7, 2008 Accepted June 16, 2008 Dietary flavonoids inhibit the anti-cancer effects of the proteasome inhibitor Bortezomib Feng-Ting Liu, Samir G Agrawal, Zanyar Movasaghi, Peter B Wyatt, Ihtesham U Rehman, John G Gribben, Adrian C. Newland, and Li Jia* Centre for Haematology, Institute of Cell and Molecular Science, Queen Mary University of London, London, United Kingdom Department of Materials /IRC, Biomedical Materials, Queen Mary University of London, London, United Kingdom School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom Centre for Experimental Cancer Medicine, Institute of Cancer, Queen Mary University of London, London, United Kingdom * Corresponding author; email: l.jia{at}qmul.ac.uk. Dietary flavonoids have many health-promoting actions, including anti-cancer activity via proteasome inhibition. Bortezomib is a dipeptide boronate proteasome inhibitor that has activity in the treatment of multiple myeloma, but is not effective in chronic lymphocytic leukemia (CLL). Although CLL cells are sensitive in vitro to Bortezomib-induced apoptosis when cultured in medium, the killing activity was blocked when cultured in 50% fresh autologous plasma. Dietary flavonoids, quercetin and myricetin, which are abundant in plasma, inhibited Bortezomib-induced apoptosis of primary CLL and malignant B-cell lines in a dose-dependent manner. This inhibitory effect was associated with chemical reactions between quercetin and the boronic acid group, -RB(OH)2, in Bortezomib. The addition of boric acid diminished the inhibitory effect of both quercetin and plasma on Bortezomib-induced apoptosis. The protective effect was also reduced when myeloma cell lines, but not B-cell lines, were pre-incubated with quercetin, indicating a direct effect of quercetin on myeloma cells. At high doses, quercetin itself induced tumor cell death. This data indicates that dietary flavonoids limit the efficacy of Bortezomib, while supplemental inorganic boric acid is able to reverse this. The complex interactions between quercetin, tumor cells and Bortezomib mean caution is required when giving dietary advice to patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Why is CLL refractory to bortezomib? Ranmohan Gitendra Wickremasinghe Blood 2008 112: 3540-3541. [Full Text] [PDF] This article has been cited by other articles: J. J. Shah, D. J. Kuhn, and R. Z. Orlowski Bortezomib and EGCG: no green tea for you? Blood, June 4, 2009; 113(23): 5695 - 5696. [Full Text] [PDF] E. B. Golden, P. Y. Lam, A. Kardosh, K. J. Gaffney, E. Cadenas, S. G. Louie, N. A. Petasis, T. C. Chen, and A. H. Schonthal Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors Blood, June 4, 2009; 113(23): 5927 - 5937. [Abstract] [Full Text] [PDF]

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