Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2015; 7(2): 418-427
Published online Mar 26, 2015. doi: 10.4252/wjsc.v7.i2.418
Mitochondria as therapeutic targets for cancer stem cells
In Sung Song, Jeong Yu Jeong, Seung Hun Jeong, Hyoung Kyu Kim, Kyung Soo Ko, Byoung Doo Rhee, Nari Kim, Jin Han
In Sung Song, Jeong Yu Jeong, Seung Hun Jeong, Hyoung Kyu Kim, Kyung Soo Ko, Byoung Doo Rhee, Nari Kim, Jin Han, National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, South Korea
Author contributions: Song IS, Ko KS, Rhee BD, Kim N and Han J conceived and designed the review; Jeong JY, Jeong SH and Kim HK searched and analyzed the references; Song IS and Han J wrote the paper.
Supported by A grant from a Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, No. 2010-0020224; and a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, No. 2012R1A1A2041700.
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: Jin Han, MD, PhD, National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, 633-165 Gaegeum-dong, Busanjin-gu, Busan 614-735, South Korea. phyhanj@inje.ac.kr
Telephone: +82-51-8906727 Fax: +82-51-8945714
Received: July 27, 2014
Peer-review started: July 27, 2014
First decision: August 28, 2014
Revised: September 25, 2014
Accepted: October 31, 2014
Article in press: November 3, 2014
Published online: March 26, 2015
Processing time: 235 Days and 23.2 Hours
Abstract

Cancer stem cells (CSCs) are maintained by their somatic stem cells and are responsible for tumor initiation, chemoresistance, and metastasis. Evidence for the CSCs existence has been reported for a number of human cancers. The CSC mitochondria have been shown recently to be an important target for cancer treatment, but clinical significance of CSCs and their mitochondria properties remain unclear. Mitochondria-targeted agents are considerably more effective compared to other agents in triggering apoptosis of CSCs, as well as general cancer cells, via mitochondrial dysfunction. Mitochondrial metabolism is altered in cancer cells because of their reliance on glycolytic intermediates, which are normally destined for oxidative phosphorylation. Therefore, inhibiting cancer-specific modifications in mitochondrial metabolism, increasing reactive oxygen species production, or stimulating mitochondrial permeabilization transition could be promising new therapeutic strategies to activate cell death in CSCs as well, as in general cancer cells. This review analyzed mitochondrial function and its potential as a therapeutic target to induce cell death in CSCs. Furthermore, combined treatment with mitochondria-targeted drugs will be a promising strategy for the treatment of relapsed and refractory cancer.

Keywords: Cancer stem cells; Mitochondria; Relapsed and refractory cancer; Therapeutic target; Mitochondrial energy metabolism

Core tip: This review is devoted to the analysis of mitochondrial function as a therapeutic target to induce cell death in cancer stem cells (CSCs). In particular, we focused on the differences in energy metabolism and features between CSC and non-CSC mitochondria, and between CSCs and normal stem cells. We described the roles of mitochondria that may make CSCs more susceptible to anti-cancer treatment and apoptosis, and how these may be useful to develop novel strategies for cancer treatment, such as through combined therapy with specific mitochondrial-targeting drugs.