Enhancement of the photodynamic effects on human orat squamous cell carcinoma cell lines by treatment with calcipotriol

Background: 5-Aminotaevulinic acid (ALA)-based photodynamic therapy (PDT) for patients with skin and oral diseases is a highly sophisticated procedure, but the incidence of disease recurrence after treatment with ALA-based PDT is somewhat alarming. Calcipotriol, an analogue of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has been reported to regulate the proliferation and differentiation of keratinocytes. Objective: In order to obtain even greater efficacy of ALA-based PDT, we investigated the synergistic effects of calcipotriol as an adjunct to ALA-based PDT for human oral squamous cell carcinoma (SCC) cell lines. Methods: Intracellular protoporphyrin IX (PpIX) converted from exogenous ALA in SCC cell lines treated with/without calcipotriol was measured by a fluorescence-meter. Then, the in vitro effects of calcipotriol, the cyclooxygenase (COX)-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on two SCC cell lines, HSC-2 (a COX-2 high expresser) and HSC-4 (a COX-2 non-expresser), were determined by MTT assay and double-staining for annexin V and propidium iodide. Results: The concentration of intracellular PpIX was increased in four of the eight SCC cell lines (50%) treated with calcipotriol. The greatest alteration of intracellular PpIX was found in HSC-4 (1.9-fold). The combination of calcipotriol and ALA-based PDT remarkably inhibited cellular proliferation and induced cellular death of both HSC-2 and HSC-4. Whereas, this morphological damage was more serious in HSC-4 than in HSC-2. Furthermore, these effects were almost equivalent to the synergistic effect of the combination of nimesulide and ALA-based PDT on HSC-2. Conclusions: The present study suggests that treatment with calcipotriol enhances the photodynamic effects on SCC via the accumulation of exogenous ALA-dependent PPIX. (c) 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.