INVESTIGATING THE IMPACT OF METFORMIN ON PROLIFERATION IN MITOCHONDRIA-DEPLETED MDA-MB-231 BREAST CANCER. NAZAR CELL LINE

Abstract

Metformin, an antidiabetic drug that targets mitochondrial complex I, is reported to have strong anti-proliferative effects in breast cancer cell lines. It primarily targets mitochondrial metabolism and is particularly potent against triple-negative breast cancers. Hypothesis Metformin exerts distinctive effects on proliferation in mitochondria-depleted MDA-MB-231 breast cancer cell line Aims 1) To optimize the generation of mitochondria-depleted MDA-MB 231 and 2) Investigate the susceptibility of MDA MB 231 Rho0 cells to Metformin. Methods MDA-MB-231 cells were depleted of mitochondria (Rho0) and treated with increasing metformin concentrations over 24 and 48 hours. The half-maximal inhibitory concentration (IC50) was measured using the MTS Assay. Proliferation was measured by continuous monitoring using xCELLigence RTCA-technology. Additionally, ROS production was assessed on both cell lines using the DCFDA ROS production assay. Results When comparing the effects of metformin, MDA-MB-231 cells exhibited marked sensitivity characterized by reduced proliferation due to mitochondrial complex I inhibition. In contrast, MDA-MB-231 Rho0 cells, devoid of functional mitochondria, showed a significantly altered response to metformin, indicating a shift toward mitochondria-independent survival pathways or compensatory metabolic remodeling. Conclusion The observed growth retardation in Rho0 cells supports the crucial role of functional mitochondria in cancer cell proliferation