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World J Gastrointest Oncol. Mar 15, 2014; 6(3): 74-82
Published online Mar 15, 2014. doi: 10.4251/wjgo.v6.i3.74
Published online Mar 15, 2014. doi: 10.4251/wjgo.v6.i3.74
Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation
Caitlin A Schonewolf, Monal Mehta, Devora Schiff, Hao Wu, Bruce G Haffty, Salma K Jabbour, Departments of Radiation Oncology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, The Cancer Institute of New Jersey, New Brunswick, NJ 08903, United States
Vassiliki Karantza, Departments of Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, The Cancer Institute of New Jersey, New Brunswick, NJ 08903, United States
Author contributions: Schonewolf CA and Schiff D performed the majority of experiments; Mehta M and Wu H provided guidance and were also involved in editing the manuscript; Haffty BG provided financial support for this work; Karantza V and Jabbour SK designed the study and guided Schonewolf CA in writing the manuscript.
Correspondence to: Salma K Jabbour, MD, Departments of Radiation Oncology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States. jabbousk@umdnj.edu
Telephone: +1-732-2533939 Fax: +1-732-253-3953
Received: April 23, 2013
Revised: January 11, 2014
Accepted: January 15, 2014
Published online: March 15, 2014
Revised: January 11, 2014
Accepted: January 15, 2014
Published online: March 15, 2014
Core Tip
Core tip: Autophagy is implicated as a mechanism of resistance to cancer treatment. We hypothesized that chloroquine, a lysosomotropic autophagy inhibitor, would sensitize colorectal cancer (CRC) cell lines to both radiation therapy (RT) alone and concurrent chemoradiation. Our results showed that chloroquine decreased clonogenic survival of CRC cells when given in combination with RT or concurrent 5-fluorouracil and RT. Radiosensitization by chloroquine represents a novel therapeutic approach to enhance treatment efficacy in rectal cancer.