Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2020; 12(7): 562-584
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.562
Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species
Zi-Jian Zhang, Kun-Peng Wang, Jing-Gang Mo, Li Xiong, Yu Wen
Zi-Jian Zhang, Li Xiong, Yu Wen, Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Kun-Peng Wang, Jing-Gang Mo, Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, Zhejiang Province, China
Author contributions: Zhang ZJ and Wang KP contributed equally to this work; Zhang ZJ designed and wrote the paper; Wang KP edited the manuscript; all authors reviewed and revised the manuscript.
Supported by National Natural Science Foundation of China, No. 81970569 and No. 81773293; and Natural Science Foundation of Hunan Province, No. 2017SK50121.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Yu Wen, MD, Doctor, Professor, Department of General Surgery, The Second Xiangya Hospital, Central South University, No. 139, Renming Road, Changsha 410011, Hunan Province, China.
Received: February 26, 2020
Peer-review started: February 26, 2020
First decision: April 25, 2020
Revised: May 17, 2020
Accepted: May 21, 2020
Article in press: May 21, 2020
Published online: July 26, 2020

Photodynamic therapy (PDT) is an effective and promising cancer treatment. PDT directly generates reactive oxygen species (ROS) through photochemical reactions. This oxygen-dependent exogenous ROS has anti-cancer stem cell (CSC) effect. In addition, PDT may also increase ROS production by altering metabolism, endoplasmic reticulum stress, or potential of mitochondrial membrane. It is known that the half-life of ROS in PDT is short, with high reactivity and limited diffusion distance. Therefore, the main targeting position of PDT is often the subcellular localization of photosensitizers, which is helpful for us to explain how PDT affects CSC characteristics, including differentiation, self-renewal, apoptosis, autophagy, and immunogenicity. Broadly speaking, excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA, change mitochondrial permeability, activate unfolded protein response, autophagy, and CSC resting state. Therefore, understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis. In this article, we review the effects of two types of photochemical reactions on PDT, the metabolic processes, and the biological effects of ROS in different subcellular locations on CSCs.

Keywords: Cancer stem cells, Photodynamic therapy, Reactive oxygen species, Photosensitizer, Mitochondrial, Endoplasmic reticulum

Core tip: Photodynamic therapy (PDT) is an effective and promising cancer treatment. PDT directly produces reactive oxygen species (ROS) through photochemical reactions. In this article, we review the production process of oxygen-dependent exogenous ROS and the possible endogenous ROS generation process after PDT-mediated subcellular organelle stress. The intracellular metabolism of several ROS produced by PDT is analyzed. Given the extremely short half-life and limited diffusion distance of ROS, we explain from the subcellular localization of photosensitizers how PDT affects the characteristics of cancer stem cells through changes in mitochondrial permeability, activation of unfolded protein responses, autophagy and so on.