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The beta‐carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells
Author(s) -
Ma Yonggang,
Wink Michael
Publication year - 2010
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.2860
Subject(s) - harmine , abcg2 , camptothecin , mitoxantrone , pharmacology , alkaloid , p glycoprotein , atp binding cassette transporter , efflux , multiple drug resistance , chemistry , cancer cell , transporter , drug resistance , biology , cancer , biochemistry , chemotherapy , stereochemistry , genetics , microbiology and biotechnology , gene
Multidrug resistance (MDR), mediated by highly expressed ABC transporters, is one of the most important mechanisms in tumor cells. Breast cancer resistance protein (BCRP) is a member of the ABC transporter family. This transporter expels different kinds of lipophilic anticancer drugs, which have diffused into the cells. In this study, 96‐well plate based assays and flow cytometry analysis were employed to screen natural products for BCRP inhibition. The beta‐carboline alkaloid harmine inhibited BCRP in a BCRP overexpressing breast cancer cell line (MDA‐MB‐231). Harmine reduced resistance to the anticancer drugs mitoxantrone and camptothecin mediated by BCRP and might be an interesting new reversal agent. Harmine did not inhibit P‐glycoprotein (P‐gp) mediated drug efflux. Copyright © 2009 John Wiley & Sons, Ltd.