Benzo[b]Tryptanthrin Inhibits MDR1, Topoisomerase Activity, and Reverses Adriamycin Resistance in Breast Cancer Cells
- 주제(키워드) adriamycin , ATP competitive , benzo[b]tryptanthrin , MDR1 , topoisomerases
- 등재 SCIE, SCOPUS
- 발행기관 WILEY-V C H VERLAG GMBH
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000114851
- 본문언어 영어
- Published As http://dx.doi.org/10.1002/cmdc.201500068
초록/요약
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.
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