The study showed that a lab‑made form of ceramide can kill breast cancer cells with a broken p53 gene, but in cells with normal p53 it triggers a senescence‑like state that lets them avoid death. This means ceramide’s effects vary by cell type and can sometimes protect cancer cells rather than destroy them.

Ceramide is a sphingolipid which regulates a variety of signaling pathways in eukaryotic cells. Exogenous ceramide has been shown to induce cellular apoptosis. In this study, we observed that exogenous ceramide induced two distinct morphologies of cell fate following C₂-ceramide treatment between the two breast cancer cell lines MCF-7 (wild type <i>p</i>53) and MDA-MB-231 (mutant <i>p</i>53) cells. The growth assessment showed that C₂-ceramide caused significant growth inhibition and apoptosis in MDA-MB-231 cells through down-regulating the expression of mutant <i>p</i>53 whereas up-regulating the expression of pro-apoptotic Bad, and the proteolytic activation of caspase-3. However, senescence-associated (SA)-&#x3b2;-galactosidase (&#x3b2;-gal) was regulated in MCF-7 cells after C₂-ceramide treatment. The results of proliferation and apoptosis assays showed that MCF-7 cells were more resistant to C₂-ceramide treatment compared to MDA-MB-231 cells. Furthermore, C₂-ceramide treatment induced a time-responsive increase in Rb protein, a key regulator of senescence accompanied with the upregulation of both mRNA level and protein level of SA-genes PAI-1 and TGaseII in MCF-7 but not in MDA-MB-231 cells, suggesting that some cancer cells escape apoptosis through modulating senescence-like phenotype. The results of our present study depicted the mechanism of C₂-ceramide-resistant breast cancer cells, which might benefit the strategic development of ceramide-based chemotherapeutics against cancer in the future.