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Published on: June 9, 2023
Synergistic Reduction of Breast Cancer Cell Viability and Aggressiveness Through Dual Inhibition of APE1 Redox
Mariana Moreno de Sousa Rodrigues1, Priscyanne Barreto Siqueira1, Ana Clara Cavallo Dobao1
1Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcântara Gomes, Laboratório de Biologia do Câncer, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Aggressiveness and resistance to treatments are significant problems in cancer management. In this scenario, searching for new pharmacological targets for therapies is essential. The APE1 redox domain coactivates transcription factors that favor cancer malignancy. One of APE1's targets, STAT3, coordinates the transcription of genes involved in cancer hallmarks. However, the association between APE1 and STAT3 in the context of breast cancer cell survival and aggressiveness has not been previously characterized. Therefore, we investigated the role of the redox function of APE1 and STAT3 inhibitors in cell viability, proliferation, migration, invasion, and cell death. In addition, we verified the association between APE1 and STAT3 in breast cancer patient samples from TCGA and their relationship with proliferation and metastasis. Our results suggest that combined treatment with APE1 and STAT3 inhibitors can further synergistically reduce cell viability, proliferation, migration, and invasion, compared to treatment with inhibitors alone. Moreover, the APE1 and STAT3 activity levels positively correlated with proliferation and metastasis gene signatures. Thus, we suggest the APE1 redox domain and STAT3 as promising targets for new therapy strategies against breast cancer.
Insights
Targeting the APE1 redox domain and STAT3 shows promise for breast cancer therapy. Combined inhibitors synergistically reduce cancer cell survival, proliferation, migration, and invasion, offering new treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer aggressiveness and treatment resistance necessitate novel therapeutic targets.
- The APE1 redox domain influences transcription factors promoting cancer.
- STAT3, a target of APE1, regulates genes critical for cancer hallmarks.
Purpose of the Study:
- To investigate the role of APE1 redox function and STAT3 in breast cancer cell survival and aggressiveness.
- To evaluate the combined effect of APE1 and STAT3 inhibitors on breast cancer cell behavior.
- To correlate APE1 and STAT3 expression with proliferation and metastasis in patient samples.
Main Methods:
- Assessed cell viability, proliferation, migration, invasion, and cell death using APE1 and STAT3 inhibitors.
- Analyzed breast cancer patient data from TCGA to verify APE1-STAT3 association.
- Correlated APE1 and STAT3 activity with proliferation and metastasis gene signatures.
Main Results:
- Combined APE1 and STAT3 inhibition synergistically decreased breast cancer cell viability, proliferation, migration, and invasion.
- Higher APE1 and STAT3 activity levels correlated positively with proliferation and metastasis gene signatures.
- The association between APE1 and STAT3 in breast cancer aggressiveness was characterized.
Conclusions:
- The APE1 redox domain and STAT3 are potential therapeutic targets for breast cancer.
- Combined inhibition strategies targeting APE1 and STAT3 show enhanced efficacy.
- This study provides a basis for developing new targeted therapies against breast cancer.
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