Benzo[b]tryptanthrin inhibits MDR1, topoisomerase activity, and reverses adriamycin resistance in breast cancer cells

Kyu Yeon Jun, So Eun Park, Jing Lu Liang, Yurngdong Jahng, Youngjoo Kwon

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Tryptanthrin is an indoloquinazoline alkaloid isolated from indigo. Tryptanthrin and its benzo-annulated derivative, benzo[b]tryptanthrin, inhibit both topoisomerases I (topo I) and II (topo II) and cause cytotoxicity in several human cancer cell lines. From diverse assessment methods, including cleavage complex stabilization, comet, DNA unwinding/intercalation, topo II ATPase inhibition, ATP competition for topo II, and wound-healing assays, we determined that the mode of action of benzo[b]tryptanthrin is as a DNA non-intercalative and ATP-competitive topo I 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 protein 1 (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..

Original languageEnglish
Pages (from-to)827-835
Number of pages9
Issue number5
StatePublished - 1 May 2015

Bibliographical note

Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


  • ATP competitive
  • MDR1
  • adriamycin
  • benzo[b]tryptanthrin
  • topoisomerases


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