The role of short-chained ceramides on breast cancer cellular trafficking

Abstract

Breast cancer is one of the leading causes of cancer-related mortality worldwide, highlighting the need for new therapeutic strategies. Ceramides, key metabolites of sphingolipid metabolism, are involved in apoptosis, mitochondrial regulation, and cellular stress responses. This study investigated the effects of short-chain C6-ceramide on mitochondrial function in MDA-MB-231 and MCF7 breast cancer cell lines. Cell viability was assessed using the MTS assay, while mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) production were analyzed by flow cytometry using TMRM and MitoSOX staining. Comparative gene expression analysis related to mitochondrial function and apoptosis was also performed. The results demonstrated that C6-ceramide reduced cell viability in a dose-dependent manner in both cell lines, with MDA-MB-231 cells showing greater sensitivity. C6-ceramide also induced mitochondrial depolarization and increased oxidative stress, particularly in MDA-MB-231 cells. Gene expression analysis suggested that these differences may be associated with higher expression of apoptosis- and mitochondrial-related genes in MDA-MB-231 cells, while MCF7 cells showed higher expression of anti-apoptotic genes such as BCL2. Overall, the findings suggest that C6-ceramide promotes mitochondrial dysfunction and oxidative stress in breast cancer cells, supporting its potential therapeutic role in aggressive breast cancer subtypes.