Natural polyphenols antagonize the antimyeloma activity of proteasome inhibitor bortezomib by direct chemical interaction

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Title
Natural polyphenols antagonize the antimyeloma activity of proteasome inhibitor bortezomib by direct chemical interaction
Author(s)
T Y Kim; J Park; B Oh; H J Min; Tae Sook Jeong; J H Lee; C Suh; J W Cheong; H J Kim; S S Yoon; S B Park; D S Lee; KMMWP
Bibliographic Citation
British Journal of Haematology, vol. 146, no. 3, pp. 270-281
Publication Year
2009
Abstract
Bortezomib is a therapeutic proteasome inhibitor with antimyeloma activity and polyphenols are well known compounds that exert antiproliferative effects against tumuors. We attempted to co-treat myeloma cells with bortezomib and polyphenols, anticipating a synergistic effect. However, the anticancer activity of bortezomib was blocked by the polyphenols. The structural features of the polyphenols correlated strikingly with their antagonistic effect; in particular, the presence or absence of a vicinal diol moiety was the key element for effective blockage of the anticancer function of bortezomib. We speculated that the vicinal diols in the polyphenols interact with the boronic acid of bortezomib and convert the active triangular boronic acid of bortezomib to an inactive tetrahedral boronate, thus abolishing the antimyeloma activity of bortezomib. We confirmed this hypothesis by 11B nuclear magnetic resonance spectroscopy and an in vitro assay on multiple myeloma (MM) cell lines and primary myeloma cells from patients. Based on these findings, restriction of the intake of natural polyphenols in foods or vitamin supplements during bortezomib treatment in MM patients should be considered.
Keyword
bortezomibpolyphenolsmultiple myelomadrug-drug interactionvicinal diol
ISSN
0007-1048
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/j.1365-2141.2009.07752.x
Type
Article
Appears in Collections:
Division of Biomaterials Research > Industrial Bio-materials Research Center > 1. Journal Articles
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