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Natural polyphenols antagonize the antimyeloma activity of proteasome inhibitor bortezomib by direct chemical interaction
프로테아좀 억제제 보르테조밉과 천연 폴리페놀의 직접 화학상호작용에 의한 길항작용

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Authors
김태영
Advisor
이동순
Major
의과대학 의학과
Issue Date
2013-02
Publisher
서울대학교 대학원
Keywords
bortezomibpolyphenolsmultiple myelomadrug-drug interactionvicinal diol
Description
학위논문 (박사)-- 서울대학교 대학원 : 의학과 분자종양의학 전공, 2013. 2. 이동순.
Abstract
Bortezomib is a therapeutic proteasome inhibitor with antimyeloma activity and polyphenols are well known compounds exerting antiproliferative effects against tumors. We attempted cotreatment of 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 infer 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, which abolishes the antimyeloma activity of bortezomib. We confirmed this hypothesis by 11B NMR spectroscopy and an in vitro assay on myeloma 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 multiple myeloma patients should be considered.
Language
English
URI
https://hdl.handle.net/10371/121902
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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