Insight into the Web of Stress Responses Triggered at Gene Expression Level by Porphyrin-PDT in HT29 Human Colon Carcinoma Cells

Abstract

Photodynamic therapy (PDT), a highly targeted therapy with acceptable side effects, has emerged as a promising therapeutic option in oncologic pathology. One of the issues that needs to be addressed is related to the complex network of cellular responses developed by tumor cells in response to PDT. In this context, this study aims to characterize in vitro the stressors and the corresponding cellular responses triggered by PDT in the human colon carcinoma HT29 cell line, using a new asymmetric porphyrin derivative (P2.2) as a photosensitizer. Besides investigating the ability of P2.2-PDT to reduce the number of viable tumor cells at various P2.2 concentrations and fluences of the activating light, we assessed, using qRT-PCR, the expression levels of 84 genes critically involved in the stress response of PDT-treated cells. Results showed a fluence-dependent decrease of viable tumor cells at 24 h post-PDT, with few cells that seem to escape from PDT. We highlighted following P2.2-PDT the concomitant activation of particular cellular responses to oxidative stress, hypoxia, DNA damage and unfolded protein responses and inflammation. A web of inter-connected stressors was induced by P2.2-PDT, which underlies cell death but also elicits protective mechanisms that may delay tumor cell death or even defend these cells against the deleterious effects of PDT.

Design of A3B-Porphyrin Conjugates with Terpyridine as Potential Theranostic Agents: Synthesis, Complexation with Fe(III), Gd(III), and Photodynamic Activity

“…Synthesis. Meso- arylporphyrins have long been known to be promising agents for PDT [ 35 , 36 ]. For most of them, however, problems associated with the hydrophobicity of these structures remain.…”

Porphyrin Macrocycles: General Properties and Theranostic Potential

“…In vitro biological studies performed on various cell lines (human colon carcinoma HT-29 cells, mouse L929 fibroblasts, peripheral blood mononuclear cells, human normal dermal HS27 cells, HaCaT keratinocytes, human peripheral blood SC monocytes) confirmed good biocompatibility for these asymmetrical structural configurations [ 160 , 161 , 168 ]. Furthermore, new amphiphilic porphyrins generated important amounts of singlet oxygen when activated with light at 635 nm [ 161 , 181 ].…”

“…In a recent study, one of the A3B-type asymmetric structures synthesized by us was investigated in vitro for its ability to reduce the number of tumor cells by PDT. In addition, the profile of stress gene expression changes triggered in vitro by porphyrin PDT in HT-29 human colon carcinoma cells was established [ 181 ].…”

“…This web of interconnected stressors underlies cell death, but can also trigger protective mechanisms that may delay tumor cell death or even defend cells against the deleterious effects of PDT. This stress-related molecular profile allowed us to identify potential therapeutic targets, such as the cytoprotective transcription factor NRF2, which could be used to develop co-therapies aimed at increasing PDT efficacy in cancer cells or protecting normal tissues [ 181 ].…”

Study of Viral Photoinactivation by UV-C Light and Photosensitizer Using a Pseudotyped Model

“…Photodynamic therapy (PDT) is another light-based strategy that has been proposed to treat infections by damaging microorganisms, fungi, parasites, and viral particles. PDT is based on the use of photo-sensitive agents named photosensitizers (PS) which, in light-excited conditions and the presence of molecular oxygen, produce reactive oxygen species (ROS) [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. PDT may damage cells via ROS generation, causing necrosis and apoptosis without harming the neighboring tissues.…”