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

Cited 19 time in Web of Science Cited 26 time in Scopus
Authors
Kim, Tae Young; Park, Jongmin; Oh, Bora; Min, Hyun Jung; Lee, Jae Hoon; Cheong, June-Won; Yoon, Sung-Soo; Lee, Dong Soon; Park, Seung Bum; Kim, Hyo Jung; Suh, Cheolwon; Jeong, Tae-Sook
Issue Date
2009-08
Publisher
WILEY-BLACKWELL PUBLISHING, INC
Citation
BRITISH JOURNAL OF HAEMATOLOGY; Vol.146 3; 270-281
Keywords
bortezomibmultiple myelomapolyphenolsdrug-drug interactionvicinal diol
Abstract
P>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 (11)B 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.
ISSN
0007-1048
Language
English
URI
http://hdl.handle.net/10371/76257
DOI
https://doi.org/10.1111/j.1365-2141.2009.07752.x
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College of Medicine/School of Medicine (의과대학/대학원)Laboratory Medicine (검사의학전공)Journal Papers (저널논문_검사의학전공)
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