Apoptosis-associated genes related to photodynamic therapy in breast carcinomas
J C Silva1, J Ferreira-Strixino, L C Fontana
1Laboratório de Espectroscopia Vibracional Biomédica, Instituto de Pesquisa e Desenvolvimento-IP&D, Universidade do Vale do Paraíba-UNIVAP, Avenida Shishima Hifumi 2911, São José dos Campos, SP, 12244-000, Brazil.
Abstract:
The aim of this study was to find the apoptosis molecular markers involved in the cell death that might be related to photodynamic therapy (PDT) mechanisms in breast cancer. The mammary tumors were induced in 25 Sprague-Dawley female rats by a single, oral gavage of 7,12-dimethylbenz(a)anthracene (DMBA; 70 mg/kg body weight). Animals were divided into four groups: G1 (normal, without DMBA), G2 (control, without PDT treatment), G3 (euthanized 48 h after PDT), and G4 (euthanized 24 h after PDT). For PDT experiments, the photosensitizer used was Photodithazine, and 100 J/cm of light at a fluence rate of 100 mW/cm was delivered to treat lesions. A sample of each animal was investigated by quantitative real-time PCR using Rat Apoptosis RT2 Profiler™ PCR Array platform. The results showed 20 genes with differential expression between PDT and control groups. A significant upregulation was observed for pro-apoptotic genes CASP4, CASP12, CIDEA, GADD45A, and FAS and downregulation of anti-apoptotic genes MAPK8IP1, TNFRSF11B, and NAIP2 in PDT-treated tumors. These results indicate that these genes are more directly involved in cell apoptosis induced by PDT.
Insights
This study identifies key apoptosis molecular markers in breast cancer cells treated with photodynamic therapy (PDT). PDT significantly altered the expression of pro-apoptotic and anti-apoptotic genes, revealing mechanisms of cell death.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast cancer remains a significant health concern, necessitating novel therapeutic strategies.
- Photodynamic therapy (PDT) is an emerging treatment modality that utilizes photosensitizers and light to induce cancer cell death.
- Understanding the molecular mechanisms underlying PDT-induced apoptosis is crucial for optimizing its efficacy.
Purpose of the Study:
- To identify apoptosis molecular markers involved in photodynamic therapy (PDT) mechanisms in chemically induced breast cancer.
- To investigate the differential gene expression profiles in PDT-treated versus control breast tumors.
- To elucidate the role of specific pro-apoptotic and anti-apoptotic genes in PDT-mediated cell death.
Main Methods:
- Mammary tumors were induced in Sprague-Dawley rats using 7,12-dimethylbenz(a)anthracene (DMBA).
- Animals were divided into control and PDT treatment groups, with samples collected at 24 and 48 hours post-treatment.
- Quantitative real-time PCR was performed using the Rat Apoptosis RT2 Profiler™ PCR Array to analyze gene expression.
Main Results:
- Photodynamic therapy (PDT) resulted in differential expression of 20 genes between treated and control tumors.
- Significant upregulation of pro-apoptotic genes (CASP4, CASP12, CIDEA, GADD45A, FAS) was observed in PDT-treated tumors.
- Downregulation of anti-apoptotic genes (MAPK8IP1, TNFRSF11B, NAIP2) was noted in tumors receiving PDT.
Conclusions:
- The identified genes, including CASP4, CASP12, CIDEA, GADD45A, FAS, MAPK8IP1, TNFRSF11B, and NAIP2, are directly involved in PDT-induced apoptosis in breast cancer.
- These findings provide insights into the molecular pathways targeted by PDT, potentially guiding future therapeutic development.
- Further research can explore the therapeutic potential of modulating these specific apoptosis markers in breast cancer treatment.
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