Photodynamic therapy for human oral squamous cell carcinoma and xenografts using a new photosensitizer, PAD-S31.
OBJECTIVE
Photodynamic therapy (PDT) is a novel and promising cancer treatment that employs a combination of photosensitizer and visible light. We examined the effect of PDT using a new photosensitizer, PAD-S31, and the 670-nm diode laser in human oral squamous cell carcinomas (SCC).


METHODS
SAS and HSC-4 cell lines were used in all the experiments. Cell viability was determined by a modified MTT assay. Two methods were used for the determination of apoptosis in human oral SCC cells: TUNEL assay and detection of fragmented mono- and oligo-nucleosomes by ELISA. Xenografts of human oral SCC cells were generated in KSN S1c nude mice.


RESULTS
In vitro PDT using PAD-S31 and the 670-nm diode laser showed cytotoxicity that was a function of laser energy, drug concentration, and time to the SAS and HSC-4 cell lines. On the other hand, PAD-S31 without irradiation had no effect on cell viability. The combinated use of PAD-S31 and the laser irradiation showed excellent anti-tumor activity against tumor xenografts without severe side effects. PDT-mediated cell death occurred predominantly by apoptosis in vitro and in vivo.


CONCLUSIONS
The present study demonstrates that PAD-S31 may serve as a potent photosensitizer for PDT. Furthermore, it is expected that this therapy will be clinically useful for the treatment of patients with oral carcinoma.
Date
Masataka
M
Department of Pharmacology, Osaka Dental University, Hirakata 573-1121, Japan. date@cc.osaka-dent.ac.jp
Sakata
Isao
I
Fukuchi
Kazuhide
K
Ohura
Kiyoshi
K
Azuma
Yasutaka
Y
Shinohara
Mitsuko
M
Matsuzaki
Koichi
K
Namiki
Yoshihisa
Y
Takahashi
Hiroshi
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
C446480:13,17-bis(1-carboxypropionyl)carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl porphyrin; D017319:Photosensitizing Agents; D011166:Porphyrins