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.
Highlights
Non-melanoma skin cancer (NMSC) is the most frequent neoplasia worldwide [1]
We found that cell viability was significantly higher in Photodynamic therapy (PDT)-resistant HSC-1 cells than parental HSCp-a1recnetalllsc,elwls hatedrieffaersenint liPghDt Tflu-reencseiss.tIannthtiHs rSegCar-d1, lcigehlltsflauepnpceroatx4imJ/camt2eclayn 4el5im%inoatfet1h00e%ceofll population was eliminatepdar(eFntiagluHrSeC1-1Bc)e.llTs,hwehefroelads -inchPDanT-greesiisntadnet xHSoCf-1PcDelTls-arpepsriosxtaimnatteHlyS4C5%-1ofctehlelsceilsl p2o.p5u2l-aftoiolnd higher than parental cellsw(Fasigeluimreina1tCed).(FTighuersee1Br)e.sTuhletsfoaldr-echianndgeicinadtievxeofoPfDtTh-ereesimstaenrtgHeSnCc-e1 coefllsaisre2s.5i2s-tfaolndthpighheernotype in the than parental cells (Figure 1C)
Regarding the reactive oxygen species (ROS) production in parental and resistant cells post-PDT, we found a significant decrease in the production of ROS in resistant HSC-1 compared to parental cells in condition no treatment (NT) or methyl aminolevulinate (MAL) incubation (Figure 3E)
Summary
Basal cell carcinomas comprise about 80% of NMSC. The remaining 20% correspond to squamous cell carcinomas (SCC) [2], which may be preceded by actinic keratosis (AK) or Bowen’s disease (BD) [3]. Conventional treatment methods for SCC, AK and BD include surgery and non-surgical therapies such as curettage, electrodessication and cryotherapy [4,5]. PDT is a treatment that combines the use of light, a photosensitizer (PS), and oxygen of the cells. The mechanism of PDT action starts when the PS enters and accumulates into cell, to be excited by light at a specific wavelength [7]. Excited PS transfers energy to cellular oxygen, producing reactive oxygen species (ROS), mainly singlet oxygen (1O2) [8]. The ROS triggers cell death by apoptosis [9], autophagy, and/or necrosis [7] selectively in those cells which incorporated the PS molecules [10]
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