Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells.

Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Research Abstract Details 

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Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Abstract Text:

Hisakazu Ohtani,Tomomi Ikegawa,Youko Honda,Noriko Kohyama,Satoshi Morimoto,Yukihiro Shoyama,Motoharu Juichi,Mikihiko Naito,Takashi Tsuruo,Yasufumi Sawada,

PURPOSE: Some methoxyflavones (MFs) are known to inhibit the function of P-glycoprotein. The aim of this study is to characterize the reversal of multidrug resistance (MDR) by MFs. METHODS: The effects of 19 MFs, including 3,5,6,7,8,3',4'-heptamethoxyflavone, nobiletin, and tangeretin, and flavone on the uptake of [3H]vincristine into an adriamycin-resistant variant of human chronic myelogenous leukemia (K562/ADM) cells were investigated. Potentiation of vincristine-induced growth inhibition by these MFs was also tested in K562/ADM cells by means of WST-1 [2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium] assay. RESULTS: All MFs (20 microM) tested increased the uptake of [3H]vincristine. 3,5,6,7,8,3',4'-heptamethoxyflavone, nobiletin, tangeretin, quercetagetin and quercetin pentamethylether showed especially potent effects. The increase in the uptake of [3H]vincristine was proportional to the number of methoxyl moieties. While substitution with a methoxyl moiety at the C3 position was the most influential, methoxyl substitution at both the C3' and C5' positions resulted in a decrease in the potentiation of uptake. Furthermore, there was a significant correlation between the potencies for increasing [3H]vincristine uptake and for growth inhibition assessed by WST-1 assay. CONCLUSIONS: MFs increased the uptake of [3H]vincristine into MDR cells and exhibited MDR-reversing effects. Their potencies were influenced by the number and positions of the methoxyl moieties.

Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Publishing Authors By Initials

H Ohtani,T Ikegawa,Y Honda,N Kohyama,S Morimoto,Y Shoyama,M Juichi,M Naito,T Tsuruo,Y Sawada,

For similar heterocyclic compounds: alkaloids: indole alkaloids: secologanin tryptamine alkaloids: vinca alkaloids: vincristine research abstracts see: heterocyclic compounds: alkaloids: indole alkaloids: secologanin tryptamine alkaloids: vinca alkaloids: vincristine research

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Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Pharmaceutical research

VOLUME: 24

Page Numbers: 1936-43

Journal Abbreviation: Pharm. Res.

ISSN: 0724-8741

DAY: 10

MONTH: 05

YEAR: 2007

Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Information

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LANGUAGE: eng

NlmUniqueID: 8406521

Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Keywords Mesh Terms:

KEYWORDS: Vincristine

MESH TERMS: metabolism

Chemical & Substance for Abstract: Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells. Information

Substance Name: Vincristine

Registry Number: 57-22-7

Grant and Affiliation Information for Effects of various methoxyflavones on vincristine uptake and multidrug resistance to vincristine in P-gp-overexpressing K562/ADM cells.

AFFILIATION: Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Country: United States

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MEDLINETA: Pharm Res

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