This study compares the effects of the biguanides metformin and phenformin on autophagy-related processes in breast cancer cells, focusing on their potential as metabolic modulators in cancer therapy. Breast cancer cell lines were treated with metformin or phenformin. Cell viability was assessed using the MTT assay. Western blotting was performed to evaluate autophagy- and mitochondrial quality-control-related protein expression (LC3B, p62, COX6, PINK1). Lipid droplet–lysosome colocalization was analyzed by fluorescence microscopy, and flow cytometry was used to monitor cellular metabolic changes.
Phenformin exhibited a stronger antiproliferative effect than metformin. Phenformin-treated cells showed greater modulation of autophagy-associated markers and increased lipid droplet–lysosome colocalization, suggesting enhanced lipid remodeling. Flow cytometry confirmed more pronounced cellular alterations with phenformin.
These preliminary results indicate that phenformin triggers stronger autophagy-related responses than metformin in breast cancer cells. Further studies will assess autophagic flux and employ mechanistic inhibition approaches to clarify phenformin’s potential as a selective metabolic modulator in breast cancer.