Benzo[b]Tryptanthrin Inhibits MDR1, Topoisomerase Activity, and Reverses Adriamycin Resistance in Breast Cancer Cells

Title
Benzo[b]Tryptanthrin Inhibits MDR1, Topoisomerase Activity, and Reverses Adriamycin Resistance in Breast Cancer Cells
Author(s)
장영동권영주[권영주]전규연[전규연]박소은[박소은]량경록
Keywords
ATOMIC PHYSICOCHEMICAL PARAMETERS; POLYGONUM-TINCTORIUM LOUR; DNA TOPOISOMERASE; QUANTITATIVE STRUCTURE; DOWN-REGULATION; LEUKEMIA-CELLS; P-GLYCOPROTEIN; TRYPTANTHRIN; AGENTS; EXPRESSION
Issue Date
201505
Publisher
WILEY-V C H VERLAG GMBH
Citation
ChemMedChem, v.10, no.5, pp.827 - 835
Abstract
Tryptanthrin is an indoloquinazoline alkaloid isolated from indigo. Tryptanthrin and its benzo-annulated derivative, benzo[b]tryptanthrin, inhibit both topoisomerasesI (topoI) and II (topoII) and cause cytotoxicity in several human cancer cell lines. From diverse assessment methods, including cleavage complex stabilization, comet, DNA unwinding/intercalation, topoII ATPase inhibition, ATP competition for topoII, and wound-healing assays, we determined that the mode of action of benzo[b]tryptanthrin is as a DNA non-intercalative and ATP-competitive topoI and II dual catalytic inhibitor. Benzo[b]tryptanthrin induced apoptosis through the cleavage of caspase-3 and PARP in HCT15 colon cancer cells. Additionally, benzo[b]tryptanthrin reversed adriamycin resistance by down-regulation of multidrug resistance protein1 (MDR1) in adriamycin-resistant MCF7 breast cancer cells (MCF7adr) with more potent inhibitory activity than tryptanthrin. Taken together, derivatization by benzo-annulation of tryptanthrin ameliorated the MDR-reversing effect of tryptanthrin and may pave the way to the discovery of a novel potent adjuvant agent for chemotherapy.
URI
http://hdl.handle.net/YU.REPOSITORY/32490http://dx.doi.org/10.1002/cmdc.201500068
ISSN
1860-7179
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약학대학 > 약학부 > Articles
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