Dual Inhibition of PARP and Akt Induces Metabolic Collapse and Apoptosis in Breast Cancer Cells.

backgroundBreast cancer is the most prevalent cancer among women worldwide, and therapeutic resistance represents a major clinical challenge. Mitochondria are key regulators of cancer metabolism, redox homeostasis, and apoptosis, making them potential therapeutic targets.

aimThis study aimed to evaluate the effects of combined Akt and PARP inhibition on mitochondrial metabolic function, energy production, and apoptosis in breast cancer cells. METHODOLOGY: The SRB assay was used to compare the viability of MDA-MB-231 and MCF7 cells. A colony formation assay was conducted to assess the capacity of individual cells to develop colonies, and ROS production was quantified using DHR123. Flow cytometric analysis was performed to evaluate cell death, and the Seahorse Mito stress test was used to measure ATP production and essential mitochondrial parameters.

resultsThe combination of Akt and PARP inhibitors impaired oxidative phosphorylation without inducing a compensatory shift to glycolysis, leading to reduced ATP production, increased ROS generation, and apoptotic cell death in breast cancer cells compared to monotherapy. CONCLUSIONS AND RECOMMENDATIONS: These findings indicate that the combination of olaparib and capivasterib is a promising therapeutic strategy for breast cancer. Furthermore, evaluation of in vivo toxicity and antitumor effectiveness is essential to validate its potential.