2-epi-Jaspine B induces mitochondria-mediated and autophagic cell death via ceramide overload in a cervical cancer model

Marine-derived sphingolipids exhibit diverse biological activities, including notable anticancer properties that have recently garnered increasing scientific interest. This study aimed to evaluate the antiproliferative activity of a newly synthesized compound, 2-epi-jaspine B hydrochloride (M1), a cyclic anhydrophytosphingosine derivative, in an in vitro model using human cervical carcinoma (HeLa) cells. The antiproliferative effect of M1 was assessed via the MTS metabolic assay, which yielded an IC₅₀ value of 5.6 ± 0.32 µmol/l. Flow cytometry and Western blot analyses demonstrated that M1 effectively induced both intrinsic and extrinsic apoptotic pathways, along with autophagic cell death. These effects were mediated through modulation of sphingolipid metabolism, resulting in the accumulation of ceramide, a key pro-apoptotic lipid. Our findings highlight the multiple mechanisms of action of M1 and its significant potential as an anticancer agent. By targeting sphingolipid metabolic pathways, 2-epi-jaspine B not only impairs cell proliferation but also triggers programmed cell death through multiple pathways. These results support the potential of marine-derived sphingolipid analogs, such as M1, for future development as therapeutic agents in the treatment of cervical cancer and possibly other malignancies.