Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Abstract

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.

Transcriptional Regulation of the Colorectal Cancer Stem Cell Markers, Nanog and Oct4, Induced by a Thermodynamic-Based Therapy Approach

“…This nding is similar to previous studies who reported a bene cial role for PDT in treating several types of cancer including including glioblastomas, lung, esophageal, bladder, colorectal and nasopharyngeal carcinomas [32]. PDT-generated ROS can change the activity of CSC markers Oct4 and Sox2 [21]. Furthermore, ROS attacks DNA causing point mutations in key genes such as Ras [33] and p53 [34] which regulate several pathways in the cell including regulate proliferation, differentiation and apoptosis [35].…”

“…ROS can unbalance redox system as well as damage DNA and protein. Moreover, PDT can dysregulate mitochondrial activity, autophagy, and CSCs dormancy [21]. One of the most studied photosensitizer is curcumin (Cur) which has numerous therapeutic properties.…”

Epigenetic Regulation and Nonepigenetic Mechanisms of Ferroptosis Drive Emerging Nanotherapeutics in Tumor

“…Targeted photosensitizers are used in lesions to accept the corresponding wavelength of visible optical irradiation. After stimulation, the energy transfer, and electron transfer process, the surrounding oxygen molecules with chemical properties of singlet oxygen, superoxide free radicals, and reactive oxygen species, such as material and substrate molecule free radicals, are applied to biological macromolecules, eventually lead to death or apoptosis of tumor cells [ 94 ]. The fully active MOF triggers the ferroptosis mechanism to facilitate photodynamic antitumor therapy (a fully active MOF nanocarrier contains disulfide, which is used to encapsulate the photosensitizer Ce6).…”

Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

“…PDT is regarded as a minimally invasive therapeutic tool which incorporates photosensitizers and light of a specific wavelength. PDT increases endogenous ROS production via regulation of mitochondrial membrane potential [ 141 ]. PDT has a beneficial impact on various pathological conditions.…”