Two
anticancer agents, LCL85 and
photodynamic therapy (
PDT) were combined to test whether the combination
PDT/LCL85 evokes changes in the
sphingolipid (SL) profile and promotes cell death. Treatment of SCCVII mouse
squamous carcinoma cells using the
silicone phthalocyanine Pc 4 for
PDT induced increases in the prodeath global
ceramides/dihydroceramides (DHceramides), and no changes in the prosurvival
sphingosine-1-phosphate (S1P). In contrast, after LCL85, the levels of most
ceramides and DHceramides were reduced, whereas the levels of S1P were increased. After
PDT/LCL85 the levels of global
ceramides and DHceramides, and of S1P, were restored to resting levels.
PDT/LCL85 also enhanced the levels of C18-, C20-, and C20:1-
ceramide, and C18-DHceramide. Treatment with
PDT, with or without LCL85, led to substantial reductions in
sphingosine levels.
PDT/LCL85 induced enhanced autophagy and
caspase-3 activation. None of the treatments affected short-term viability of cells. In contrast, long-term clonogenic survival was reduced not only after
PDT or LCL85, but even more after
PDT/LCL85. Overall, our data show that short-term exposure to
PDT/LCL85 led to distinct signature effects on the SL profile, enhanced autophagy, and
caspase-3 activation without cell death. Long-term exposure to
PDT/LCL85 enhanced overall cell killing, supporting translational potential of
PDT/LCL85.