Cervical cancer remains one of the leading causes of cancer-related mortality among women worldwide. The prognosis of cervical cancer is poor due to persistent chemotherapy resistance and repeated recurrence; therefore the development of new drugs is crucial. CeY-B1 is a ceramide analogue that we synthesized and evaluated in cervical cancer cell lines using cell viability assays, colony formation, migration, invasion, apoptosis, and cell cycle assays. We performed lipidomics analysis to assess changes in sphingolipid metabolism after CeY-B1 treatment. Furthermore, we conducted network pharmacology analysis to predict potential molecular targets and signaling pathways. We further detected key signaling proteins using qPCR and Western blot analysis. Finally, we evaluated the antitumor efficacy of CeY-B1 in a subcutaneous xenograft mouse model. In this study, we synthesized a ceramide analog CeY-B1, which inhibited the proliferation, migration, and invasion of cervical cancer cells, induced apoptosis and cell cycle arrest, and suppressed tumor growth in a xenograft mouse model. Lipidomics results showed that CeY-B1 treatment led to the accumulation of specific ceramide species, especially Cer(t18:0/24:1), Cer(t18:0/24:0), and Cer(d18:1/24:0(2OH)), indicating that the sphingolipid signaling pathway was activated. Network pharmacology revealed 78 common target genes between CeY-B1 and cervical cancer, and identified enriched pathways including PI3K/AKT signaling, MAPK signaling, and oxidative stress response. Mechanistic studies showed that CeY-B1 upregulated ASK1 and phosphorylated JNK while downregulated Bcl-2. Lipid sequencing and network pharmacology showed that the ASK1-JNK pathway was activated and the PI3K/AKT pathway was inhibited in the sphingolipid signaling cascade, both of which contribute to cell apoptosis. These findings support the potential of CeY-B1 as a novel therapeutic agent for cervical cancer, via the regulation of ceramide metabolism, cell survival, and apoptotic pathways.
Tang et al. (Sat,) studied this question.