[2] However, preclinical and clinical studies have shown that combining safingol with conventional chemotherapy agents such as fenretinide, vinblastine, irinotecan and mitomycin C can dramatically potentiate their antitumor effects.

Safingol competitively competes with phorbol dibutyrate at regulatory domains of the protein kinase C family, inhibiting the activation of such enzymes as PKCβ-I, PKCδ, and PKCε.

[3] One potential explanation for safingol’s cytotoxicity is that high concentrations result in ROS-related molecular and cellular damage that is beyond repair.

However, not only does this hypothesis warrants further testing, but safingol has demonstrated unusual regulatory effects on other pathways capable of regulating autophagy.

Modulations in Bcl-2, Bcl-xL, and endonuclease G from mitochondria are also thought to play a role in safingol-induced cellular death by regulating autophagy.

It can also affect the balance of other endogenous sphingolipids, particularly ceramide and dihydroceramide, which have been implicated in autophagic induction[6] and ROS production.