Next Article in Journal
Living Organisms Author Their Read-Write Genomes in Evolution
Previous Article in Journal
Dual Roles of Fer Kinase Are Required for Proper Hematopoiesis and Vascular Endothelium Organization during Zebrafish Development
Article Menu

Export Article

Open AccessCommunication
Biology 2017, 6(4), 41; doi:10.3390/biology6040041

Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in Cancer Cells

1
Cancer Research Laboratory, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
2
Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA
3
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
4
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
5
Center for Genome Research and Biocomputing, Oregon State University, Corvallis, OR 97331, USA
Current address: Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA.
*
Author to whom correspondence should be addressed.
Academic Editor: Jukka Finne
Received: 30 September 2017 / Revised: 14 November 2017 / Accepted: 22 November 2017 / Published: 1 December 2017
View Full-Text   |   Download PDF [2171 KB, uploaded 1 December 2017]   |  

Abstract

We previously reported that raloxifene, an estrogen receptor modulator, is also a ligand for the aryl hydrocarbon receptor (AhR). Raloxifene induces apoptosis in estrogen receptor-negative human cancer cells through the AhR. We performed structure–activity studies with seven raloxifene analogs to better understand the structural requirements of raloxifene for induction of AhR-mediated transcriptional activity and apoptosis. We identified Y134 as a raloxifene analog that activates AhR-mediated transcriptional activity and induces apoptosis in MDA-MB-231 human triple negative breast cancer cells. Suppression of AhR expression strongly reduced apoptosis induced by Y134, indicating the requirement of AhR for Y134-induced apoptosis. Y134 also induced apoptosis in hepatoma cells without having an effect on cell cycle regulation. Toxicity testing on zebrafish embryos revealed that Y134 has a significantly better safety profile than raloxifene. Our studies also identified an analog of raloxifene that acts as a partial antagonist of the AhR, and is capable of inhibiting AhR agonist-induced transcriptional activity. We conclude that Y134 is a promising raloxifene analog for further optimization as an anti-cancer agent targeting the AhR. View Full-Text
Keywords: aryl hydrocarbon receptor; raloxifene; Y134; estrogen receptor modulator; hepatoma; agonist; antagonist; anti-cancer drug; triple negative breast cancer; apoptosis aryl hydrocarbon receptor; raloxifene; Y134; estrogen receptor modulator; hepatoma; agonist; antagonist; anti-cancer drug; triple negative breast cancer; apoptosis
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Jang, H.S.; Pearce, M.; O’Donnell, E.F.; Nguyen, B.D.; Truong, L.; Mueller, M.J.; Bisson, W.H.; Kerkvliet, N.I.; Tanguay, R.L.; Kolluri, S.K. Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in Cancer Cells. Biology 2017, 6, 41.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top