Multi-Target Inhibitor CUDC-101 Impairs DNA Damage Repair and Enhances Radiation Response in Triple-Negative Breast...

Area of Science:

• Oncology
• Radiation Oncology
• Molecular Biology

Background:

• Histone deacetylase inhibitors (HDACi) are known to improve radiation response in breast cancer.
• Research on combining HDAC inhibitors with proton radiation is limited.
• CUDC-101 is a novel inhibitor targeting HDACs, EGFR, and HER-2.

Purpose of the Study:

• To evaluate CUDC-101's efficacy in enhancing responses to proton and X-ray irradiation.
• To investigate CUDC-101's effects on breast cancer cell lines, including triple-negative subtypes.

Main Methods:

• MCF-7, MDA-MB-231, and MCF-10A cell lines were pre-treated with CUDC-101.
• Cells were exposed to 148 MeV protons or X-rays.
• Assays included colony survival, γ-H2AX foci, apoptosis, and cell cycle analysis.

Main Results:

• MDA-MB-231 cells showed increased sensitivity to CUDC-101 compared to MCF-7 cells.
• CUDC-101 pre-treatment enhanced radiation-induced apoptosis in all tested cell lines.
• CUDC-101 and X-ray combination led to increased G2/M arrest in MDA-MB-231 cells.

Conclusions:

• CUDC-101 effectively enhances the response to both proton and X-ray irradiation in triple-negative MDA-MB-231 cells.
• The combination of CUDC-101 with proton irradiation showed the most significant enhancement.
• CUDC-101 demonstrates potential as a therapeutic agent for triple-negative breast cancer, alone or with radiation.