Epigallocatechin Gallate Enhances MAL-PDT Cytotoxic Effect on PDT-Resistant Skin Cancer Squamous Cells

Abstract

Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.

Assessment of natural antioxidants' effect on PDT cytotoxicity through fluorescence microscopy image analysis

“…17,37 Vitamin E (α-tocopherol) in combination with PDT, increased PDT cytotoxicity, in a concentration and incubation timedependent manner. 15 Recently, León et al 18 reported that epigallocatechin gallate catechin enhanced MAL-PDT in resistant skin cancer squamous cells.…”

“…Results have been promising, as enhancement of PDT efficacy has been shown by the addition of an antioxidant agent. [13][14][15][16][17][18][19][20] This study aimed to evaluate the enhancement of PDT efficacy through modulation of the intracellular ROS levels by using natural polyphenols. Polyphenols are powerful natural antioxidants that, like any antioxidant, can exert pro-oxidant activities under certain conditions, mainly depending on their concentration.…”

“…Using antioxidants as a pro‐oxidant stimulus that could sensitize the cancerous cells to PDT has been marginally studied. Results have been promising, as enhancement of PDT efficacy has been shown by the addition of an antioxidant agent 13–20 …”

Photosensitive Chitosan-Based Injectable Hydrogel Chemically Cross-Linked by Perylene Bisimide Dopamine with Robust Antioxidant and Cytotoxicity Enhancer Properties for In Vitro Photodynamic Therapy of Breast Cancer

“…Also, free radical chemical scavengers can neutralize the generated ROS, minimizing the adverse effect of oxidative damage caused in nontarget healthy tissues. − Various antioxidant agents, such as cinnamaldehyde, ascorbate, polyphenols, and epigallocatechin gallate, have been investigated in combination with PDT. These studies have confirmed and claimed that using antioxidant inhibition along with PDT could be a promising approach to potentiate ROS-mediated anticancer treatments’ therapeutic efficacy and reduce side effects. − The most effective radical scavengers are phenolic (ArOH) antioxidants, which could control the auto-oxidation process by donating a H atom (from OH groups) to peroxy radicals (RO 2 · ) and converting them into hydroperoxide. − The antioxidant-generated phenoxy radical reacts in different ways with other proxy radicals and terminates the propagation of free radical species by forming nonradical products . Recently, a photosensitizing chitosan-based antioxidant hydrogel using tannic acid as an antioxidant cross-linking agent has been reported to effectively utilize a combination of free radical scavenging and pro-oxidant activities.…”

Photodynamic Therapy for Basal Cell Carcinoma: The Clinical Context for Future Research Priorities

“…EGCG, a nontoxic catechin found in green tea ( Camellia sinensis ), has an established place in preclinical research on cancer prevention and treatment generally, with increasing clinical applications [ 174 , 175 ]. A MAL-PDT-resistant cSCC cell model was developed showing reduced PpIX and ROS generation, but these PDT-resistant cells were resensitized by EGCG, indicating its potential as an adjuvant to MAL-PDT [ 176 ]. In other cancers, EGCG has been shown to reduce cell growth better when combined with PDT compared with either treatment separately [ 177 ].…”