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. 2022 Oct 12;7(5):637–647. doi: 10.1089/can.2021.0100

FIG. 4.

FIG. 4.

Schematic representation of 5-epi-induced ICD. 5-epi binds to and activates the cannabinoid receptors (CB1R and CB2R), and/or others. Simultaneously, 5-epi stimulates the de novo sphingolipid synthetic pathway to enhance Cer production. SphK1 and/or SphK2 attenuate the accumulation of Cer by conversion of dhSph to dhS1P and conversion of Sph to S1P. Inhibition of the SphKs, using PF-543 or other SphK inhibitors, blocks dhS1P/S1P formation leading to Cer accumulation and enhances the ICD-inducing effects of 5-epi. dhS1P, dhSph-1-phosphate; S1P, sphingosine-1-phosphate.