Induction of apoptosis in HaCaT cells by photodynamic therapy with chlorin e6 or pheophorbide a.
The two photosensitizers, chlorin e6 and pheophorbide a, were tested in an in vitro model of topical photodynamic therapy (PDT). Both dyes accumulate in HaCaT keratinocytes as verified by fluorescence measurement but pheophorbide a is enriched fivefold more strongly than chlorin e6 after 24 h. HaCaT cells are susceptible to PDT with both dyes. The phototoxicity measured by ATP bioluminescence is caused by necrosis and apoptosis depending on the photosensitizer used and the treatment modality. Chlorin e6 shows higher toxic potential because it elicits nearly 90% cell mortality 24 h after PDT comparable to pheophorbide a but with a fivefold lower rate of accumulation. These results implicate caution with topical PDT of oncologic diseases due to the risk of serious side effects on healthy skin in the course of topical photodynamic treatment. But the lack of dark toxicity and the time-dependent enrichment of both dyes in HaCaT cells are arguments for the application of these sensitizers in topical PDT of non-malign skin disorders. Further studies are necessary to discover appropriate lower doses and mechanisms of action of topical PDT with both compounds.
Radestock
A
A
Department of Dermatology and Allergology, Friedrich Schiller University Jena, Jena, Germany.
Elsner
P
P
Gitter
B
B
Hipler
U-C
UC
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002735:Chlorophyllides; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D002735:Chlorophyllides; D011166:Porphyrins; D002734:Chlorophyll; C062985:phytochlorin; D053148:Caspase 3; C032623:pheophorbide a