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

Authors
 Tae Young Kim  ;  Jongmin Park  ;  Bora Oh  ;  Hyun Jung Min  ;  Tae-Sook Jeong  ;  Jae Hoon Lee  ;  Cheolwon Suh  ;  June-Won Cheong  ;  Hyo Jung Kim  ;  Sung-Soo Yoon  ;  Seung Bum Park  ;  Dong Soon Lee 
Citation
 BRITISH JOURNAL OF HAEMATOLOGY, Vol.146(3) : 270-281, 2009 
Journal Title
BRITISH JOURNAL OF HAEMATOLOGY
ISSN
 0007-1048 
Issue Date
2009
MeSH
Antineoplastic Agents/antagonists & inhibitors* ; Apoptosis/drug effects ; Boronic Acids/antagonists & inhibitors* ; Bortezomib ; Cell Proliferation/drug effects ; Drug Interactions ; Flavonoids/pharmacology* ; Humans ; Multiple Myeloma/diet therapy* ; Phenols/pharmacology* ; Polyphenols ; Pyrazines/antagonists & inhibitors*
Keywords
bortezomib ; polyphenols ; multiple myeloma ; drug-drug interaction ; vicinal diol
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 (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.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.07752.x/abstract
DOI
10.1111/j.1365-2141.2009.07752.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105268
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