Identification of endoplasmic reticulum stress-inducing agents by antagonizing autophagy: a new potential strategy for identification of anti-cancer therapeutics in B-cell malignancies
Year: 2013
Type: article
Abstract: Emilia Mahoneya, Kami Maddocksa, Joseph Flynna, Jeffrey Jonesa, Sara L. Coleb, Xiaoli Zhangc, John C. Byrdad* & Amy J. Johnsonad*a Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USAb Campus Microscopy and Imaging Facility, The Ohio State University, Columbus, OH, USAc Center for Biostatistics, The Ohio State University, Columbus, OH, USAd Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA*These authors contributed equally to this work.Correspondence: John C. Byrd, MD, B302 Starling-Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA. Tel: (614)293-9869. E-mail: [email protected] J. Johnson, PhD, OSUCCC Bldg. Room 455C, 410 West 12th Avenue. Columbus, OH 43210, USA. Tel: (614)292-8265. E-mail: [email protected] is an accompanying commentary that discusses this paper. Please refer to the issue Table of Contents.AbstractThe endoplasmic reticulum (ER) plays a vital function in multiple cellular processes. There is a growing interest in developing therapeutic agents that can target the ER in cancer cells, inducing a stress response that leads to cell death. However, ER stress-inducing agents can also induce autophagy, a survival strategy of cancer cells. Therefore, by inhibiting autophagy we can increase the efficacy of the ER stress-inducing agents. Nelfinavir, a human immunodeficiency virus (HIV) protease inhibitor with anti-cancer properties, can induce ER stress. Nelfinavir's effects on chronic lymphocytic leukemia (CLL) are yet to be elucidated. Herein we demonstrate that nelfinavir induces ER morphological changes and stress response, along with an autophagic protective strategy. Our data reveal that chloroquine, an autophagy inhibitor, significantly increases nelfinavir cytotoxicity. These results identify a novel strategy potentially effective in CLL treatment, by repositioning two well-known drugs as a combinatorial therapy with anti-cancer properties.
Authors: Emilia Mahoney, Kami Maddocks, Joseph Flynn, Jeffrey Jones, Sara L. Cole, Xiaoli Zhang, John C. Byrd, Amy J. Johnson
Institution: The Ohio State University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2039177121