Because of the failure of single modality approaches, combination
therapy for
cancer treatment is a promising alternative.
Sphingolipid analogs, with or without anticancer drugs, can improve
tumor response. C16-pyridinium
ceramide analog
LCL30, was used in combination with
photodynamic therapy (
PDT), an anticancer treatment modality, to test the hypothesis that the combined treatment will trigger changes in the
sphingolipid profile and promote cell death. Using SCCVII mouse
squamous carcinoma cells, and the
silicone phthalocyanine Pc 4 for
PDT, we showed that combining
PDT with
LCL30 (
PDT/
LCL30) was more effective than individual treatments in raising global
ceramide levels, as well as in reducing
dihydrosphingosine levels. Unlike
LCL30,
PDT, alone or combined, increased total
dihydroceramide levels.
Sphingosine levels were unaffected by
LCL30, but were abolished after
PDT or the combination. LCL30-triggered rise in
sphingosine-1-phosphate was reversed post-
PDT or the combination.
DEVDase activation was evoked after
PDT or
LCL30, and was promoted post-
PDT/
LCL30. Neither mitochondrial depolarization nor apoptosis were observed after any of the treatments. Notably, treatment with the combination resulted in augmented overall cell killing. Our data demonstrate that treatment with
PDT/
LCL30 leads to enhanced global
ceramide levels and
DEVDase activation in the absence of apoptosis, and promotion of total cell killing.