Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Dec 10, 2015; 6(6): 299-311
Published online Dec 10, 2015. doi: 10.5306/wjco.v6.i6.299
Fluoxetine induces cytotoxic endoplasmic reticulum stress and autophagy in triple negative breast cancer
Michelle Bowie, Patrick Pilie, Julia Wulfkuhle, Siya Lem, Abigail Hoffman, Shraddha Desai, Emanuel Petricoin, Amira Carter, Adrian Ambrose, Victoria Seewaldt, Dihua Yu, Catherine Ibarra Drendall
Michelle Bowie, Siya Lem, Abigail Hoffman, Shraddha Desai, Amira Carter, Adrian Ambrose, Victoria Seewaldt, Catherine Ibarra Drendall, Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC 27710, United States
Patrick Pilie, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, United States
Julia Wulfkuhle, Emanuel Petricoin, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, United States
Dihua Yu, Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Author contributions: Bowie M, Pilie P, and Ibarra Drendall C designed the experiments; Bowie M and Ibarra Drendall C performed most of the experiments and analyzed the data; Pilie P, Seewaldt V, and Yu D conceived the project; Wulfkuhle J and Petricoin E performed the protein microarray analysis; Lem S, Desai S, and Carter A helped with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blotting; Hoffman A and Ambrose A helped with the cell lysates preparation; Ibarra Drendall C conceived and wrote the manuscript.
Supported by Susan G. Komen for the Cure Career Catalyst in Disparities Research to Ibarra Drendall C (KG090730) and Promise Grant to Yu D (KG091020); National Institute of Health to Seewaldt V (R01CA158668).
Informed consent statement: Not applicable.
Institutional animal care and use committee statement: Not applicable.
Conflict-of-interest statement: There is no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Catherine Ibarra Drendall, PhD, Assistant Professor, Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Box 2628, Durham, NC 27710, United States. cathibar02@yahoo.com
Telephone: +1-919-2746007 Fax: +1-919-6682458
Received: May 29, 2015
Peer-review started: May 31, 2015
First decision: August 11, 2015
Revised: September 8, 2015
Accepted: October 23, 2015
Article in press: October 27, 2015
Published online: December 10, 2015
Core Tip

Core tip: Our study demonstrates for the first time the complex but selective actions of Food and Drug Administration-approved, well-tolerated antidepressant drug known as fluoxetine (FLX) in malignant triple negative breast cancer (TNBC) cells. The significant reduction in cell growth of inflammatory TNBC line SUM149PT was a consequence of unfolded protein response induced by FLX and subsequent induction of autophagy and mitochondrial apoptosis, demonstrating the intricate crosstalk between endoplasmic reticulum and mitochondria in response to cellular stress. Combination of low dose FLX with existing regimen for TNBC may provide dual benefit of alleviating psychological distress, including depression and anxiety, and inducing death in aggressive tumor cells.