Enhancement of photodynamic effect in normal rat keratinocytes by treatment with 1,25 dihydroxy vitamin D3.
BACKGROUND
To better understand the pathogenesis of photodynamic therapy (PDT)-induced apoptosis cytosolic calcium [Ca2+]i was measured using cultured fetal rat keratinocytes (FRSKs). Moreover, the influence of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) with the action of increasing [Ca2+]i on the PDT effect was studied.


METHODS
FRSKs were treated with a medium containing the photosensitizer, aluminum phthalocyanine tetrasulfonate (AlPcTs), and were then exposed to selective visible light derived from a halogen lamp. Electrophoresis of DNA extracted from the PDT-treated cells revealed DNA fragmentation, a sign of apoptosis in cultured FRSKs under the condition with or without 1,25(OH)2D3.


RESULTS
PDT-treated FRSKs exhibited increased levels of [Ca2+]i; these levels were significantly elevated further by the treatment of cells with 1,25(OH)2D3. However, cells treated with ethylene glycol bis (b-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), a chelator of extracellular calcium, prior to PDT did not show any DNA fragmentation either in the presence or absence of 1,25(OH)2D3.


CONCLUSIONS
PDT-induced apoptosis in FRSKs may be caused by the influx of extracellular calcium. Addition of 1,25(OH)2D3 clearly enhanced the DNA fragmentation in the cultured FRSKs, indicating the effect of increased [Ca2+]i. The combination therapy of AlPcTs-PDT with the administration of 1,25(OH)2D3 may contribute to the enhancement of the AlPcTs-PTD effect.
Matsuyama
Asako
A
Department of Dermatology, Hirosaki University School of Medicine, Hirosaki, Japan.
Nakano
Hajime
H
Harada
Ken
K
Yamazaki
Takehiko
T
Kanno
Takahiro
T
Wakui
Makoto
M
Hanada
Katsumi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004622:Embryo, Mammalian; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D010778:Photochemotherapy; D051381:Rats; D014466:Ultraviolet Rays
D004247:DNA; D002117:Calcitriol; D002118:Calcium