Antitumor effect of photodynamic therapy with zincphyrin, zinc-coproporphyrin III, in mice.
We studied the antitumor effects of photodynamic therapy (PDT) with Zincphyrin, coproporphyrin III with zinc, derived from Streptomyces sp. AC8007, in vitro and in vivo. The photokilling effect of Zincphyrin in the presence of 0.78-100 microg/ml with visible light of 27.2 mW x min/cm2 for 10 min was lower than the hematoporphyrin (Hp) used as a control with L5178Y or sarcoma-180 cells. On the other hand, Zincphyrin apparently reduced tumor growth after intraperitoneal injection at doses of 12.5-50 mg/kg with light irradiation of 75.48 mW x min/cm2 for 10 min in sarcoma-180-bearing mice. Although no mice treated with Zincphyrin died, Hp did cause the death of mice. In B-16 melanoma-bearing mice, both Zincphyrin and Hp had a similar phototherapic effect. Further improvement of the phototherapic effect was observed with the continuous administration of Zincphyrin at 12.5 mg/kg per day for 3 days. The concentration of Zincphyrin in the serum reached a maximum level of 16 microg/ml within 20 min, and the concentration remained at 4.2 microg/ml at 1 hour after the onset of treatment, indicating its rapid action in the body. No animals died after the intraperitoneal administration of Zincphyrin at 100 mg/kg plus exposure to light of 10 mW x min/cm2 for 2 hours, and the body weight of the mice did not decrease. In contrast, all animals receiving 100 mg/kg of Hp under the same conditions died. These results indicate that Zincphyrin would be a useful photosensitizer with low phototoxicity.
Toriya
M
M
Institute for Life Science Research, Asahi Chemical Industry Co., Ltd., Tagata-gun, Shizuoka, Japan. toriya.mb@om.asahi-kasei.co.jp
Yamamoto
M
M
Saeki
K
K
Fujii
Y
Y
Matsumoto
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003306:Coproporphyrins / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity; D007940:Leukemia L5178 / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology; D014407:Tumor Cells, Cultured
D003306:Coproporphyrins; D017319:Photosensitizing Agents; C026971:coproporphyrin III