Abstract B118: PR7 rhenium complex induced cytotoxicity in triple negative breast cancer cells (TNBC) by upregulation of apoptosis-regulatory proteins gene expression

Abstract Triple-negative breast cancer (TNBC) remains the most aggressive subtype, with major obstacles to effective management necessitating a continuous search for new pharmacological agents. We investigated the cytotoxic potentials of newly synthesized rhenium complexes, PR6 and PR7, on a panel of TNBC cell lines to unravel signaling pathways mediating rhenium-induced cytotoxicity. Breast cancer cell lines (MCF-7, BT-549, MDA-MB-231, parental HCC 1806, carboplatin-resistant HCC1808 derivative, and MDA-MB-468 cells) were treated with 2.5 µM PR6 and 1.5 µM PR7 for 72 hours, and an MTS-based cell viability assay was performed. The baseline expression levels of selected metastasis-promoting proteins, including High Mobility Group AT-hook 2 (HMGA2) and phospho-AKT (p-AKT), in the parental and carboplatin-resistant HCC1806 cell lysates were determined using Western blot analysis. Additionally, the expression profiles of apoptosis-regulatory proteins, including caspases 3, 7, and 9, were determined. We found that PR7 is more potent than PR6. Furthermore, all the TNBC cell lines, including carboplatin-resistant HCC1806, were sensitive to PR7 treatment (1.5 µM). We also observed higher expression of HMGA2 and p-AKT proteins in the carboplatin-resistant HCC1806 as compared to its parental cell counterpart. Furthermore, higher expression levels of cleaved caspase 3, 7, and 9 proteins were observed in the PR6 and PR7 rhenium-treated parental HCC1806 cells and their carboplatin-resistant derivatives as compared to their corresponding DMSO control. In conclusion, rhenium compounds may be promising agents for TNBC management, including those resistant to carboplatin. Citation Format: John Abiodun. Obadipe, Santosh A. Mandal, Hwang Bor-Jang, Yusuf Mansur. Liadi, Sharma Dipali, Alexis A. Green, Valerie Odero-Marah. PR7 rhenium complex induced cytotoxicity in triple negative breast cancer cells (TNBC) by upregulation of apoptosis-regulatory proteins gene expression [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B118.