15-deoxy-Δ12,14-prostaglandin J2 induces upregulation of multidrug resistance-associated protein 1 via Nrf2 activation in human breast cancer cells

Na Young Song, Do Hee Kim, Eun Hee Kim, Hye Kyung Na, Young Joon Surh

Research output: Chapter in Book/Report/Conference proceedingConference contribution

14 Citations (Scopus)

Abstract

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ 2), a representative J-series cyclopentenone prostaglandin, exerts cytoprotective effects that are mainly mediated by Nrf2. Nrf2 is a major transcription factor involved in the transactivation of genes encoding many phase 2 detoxifying and antioxidant enzymes via interaction with the antioxidant response element (ARE). Recently it has been reported that expression of phase 3 efflux transporters, such as multidrug resistance-associated proteins (MRPs), is also regulated by Nrf2. It is well known that cancer cells overexpressing MRPs are more resistant to anticancer drugs. In the present study we have found that 15d-PGJ2 induces the expression of MRP1, one of the phase 3 efflux transporters, in human breast cancer cells (MCF-7). In addition, treatment of MCF-7 cells with 15d-PGJ2 resulted in nuclear translocation and DNA binding of Nrf2. In contrast to 15d-PGJ2, 9,10-dihydro-15d-PGJ2, an analogue of 15d-PGJ2 that lacks an electrophilic cyclopentenone ring moiety, failed to induce not only Nrf2 activation but also MRP1 upregulation in MCF-7 cells. 15d-PGJ 2-induced MRP1 overexpression was abrogated by Nrf2 gene knockdown, using RNA interference. These results, taken together, suggest that 15d-PGJ 2 induces MRP1 upregulation via Nrf2-ARE signaling.

Original languageEnglish
Title of host publicationNatural Compounds and Their Role in Apoptotic Cell Signaling Pathways
PublisherBlackwell Publishing Inc.
Pages210-216
Number of pages7
ISBN (Print)9781573317375
DOIs
Publication statusPublished - 2009 Aug

Publication series

NameAnnals of the New York Academy of Sciences
Volume1171
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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