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Photodynamic therapy reduces cell viability, migration and triggers necroptosis in prostate tumor cells
Laura Calazans de Melo Gomes1, Amanda Branquinho de Oliveira Cunha1, Luiz Felipe Fernandes Peixoto1
1Department of Cell Biology, Histology and Embryology. Institute of Biomedical Sciences-ICBIM, Federal University of Uberlândia-UFU, Uberlândia, Minas Gerais, Brazil.
Abstract:
Prostate cancer is the most common cancer in American men, aside from skin cancer. As an alternative cancer treatment, photodynamic laser therapy (PDT) can be used to induce cell death. We evaluated the PDT effect, using methylene blue as a photosensitizer, in human prostate tumor cells (PC3). PC3 were subjected to four different conditions: DMEM (control); laser treatment (L-660 nm, 100 mW, 100 J.cm-2); methylene blue treatment (MB-25 μM, 30 min), and MB treatment followed by low-level red laser irradiation (MB-PDT). Groups were evaluated after 24 h. MB-PDT treatment reduced cell viability and migration. However, because MB-PDT did not significantly increase the levels of active caspase-3 and BCL-2, apoptosis was not the primary mode of cell death. MB-PDT, on the other hand, increased the acid compartment by 100% and the LC3 immunofluorescence (an autophagy marker) by 254%. Active MLKL level, a necroptosis marker, was higher in PC3 cells after MB-PDT treatment. Furthermore, MB-PDT resulted in oxidative stress due to a decrease in total antioxidant potential, catalase levels, and increased lipid peroxidation. According to these findings, MB-PDT therapy is effective at inducing oxidative stress and reducing PC3 cell viability. In such therapy, necroptosis is also an important mechanism of cell death triggered by autophagy.
Insights
Photodynamic laser therapy using methylene blue effectively reduced prostate cancer cell viability and migration. This treatment primarily induces cell death through necroptosis and oxidative stress, rather than apoptosis.
Area of Science:
- Oncology
- Biomedical Engineering
- Photomedicine
Background:
- Prostate cancer is a prevalent malignancy in men.
- Photodynamic laser therapy (PDT) offers an alternative treatment modality for cancer by inducing cell death.
- Methylene blue (MB) serves as a photosensitizer in PDT.
Purpose of the Study:
- To evaluate the efficacy of methylene blue-based photodynamic laser therapy (MB-PDT) on human prostate cancer cells (PC3).
- To elucidate the mechanisms of cell death induced by MB-PDT in PC3 cells.
Main Methods:
- PC3 cells were exposed to four conditions: control (DMEM), laser only, MB only, and MB-PDT.
- MB-PDT involved methylene blue treatment followed by low-level red laser irradiation.
- Cell viability, migration, apoptosis markers (caspase-3, BCL-2), autophagy markers (LC3), necroptosis markers (MLKL), and oxidative stress indicators were assessed after 24 hours.
Main Results:
- MB-PDT significantly reduced PC3 cell viability and migration.
- Apoptosis was not the primary cell death mechanism, as indicated by unchanged caspase-3 and BCL-2 levels.
- MB-PDT markedly increased autophagy (LC3 by 254%) and necroptosis (MLKL), alongside significant oxidative stress (decreased antioxidants, increased lipid peroxidation).
Conclusions:
- MB-PDT is an effective treatment for reducing prostate cancer cell viability.
- The primary mechanisms of cell death induced by MB-PDT in PC3 cells are necroptosis and oxidative stress, triggered by autophagy.
- MB-PDT presents a promising therapeutic strategy for prostate cancer, warranting further investigation.
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