Enhancement of meta-tetrahydroxyphenylchlorin-sensitized photodynamic treatment on human tumor xenografts using a water-soluble vitamin E analogue, Trolox.
Photodynamic therapy (PDT) using meta-tetrahydroxyphenylchlorin (mTHPC) performed on HT29 human colon adenocarcinoma xenografts in nude mice was shown to be enhanced by Trolox, a water-soluble vitamin E analogue. Trolox, injected i.p. at 250 mg/kg body weight 90 min before PDT, delayed tumor doubling time from 13 (PDT only) to 19 days. Enhancement of the tumoricidal effect of PDT by Trolox required the presence of the drug at the photochemical stage since its injection after irradiation is ineffective. HPLC measurements indicated that 1 hr after injection the Trolox concentration in plasma was as high as 0.8 mM. In vivo measurements of mTHPC fluorescence in mice treated by PDT with or without Trolox injection showed that Trolox did not protect mTHPC from photodegradation. Laser flash photolysis studies performed in solution demonstrated that Trolox reduces triplet mTHPC efficiently (reaction rate constant 2 x 10(7) M(-1) * sec(-1)) leading to the formation of radical products. Kinetic considerations suggest that the Trolox-mediated radical pathway can work in relay with singlet oxygen in hypoxic conditions, providing a possible explanation for the observed enhancement of mTHPC-sensitized PDT by Trolox.
Melnikova
V O
VO
Unité de Recherche en Thérapie Photodynamique, Laboratoire de Recherche en Oncologie, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France.
Bezdetnaya
L N
LN
Brault
D
D
Potapenko
A Y
AY
Guillemin
F
F
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D000975:Antioxidants; D002839:Chromans; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D010100:Oxygen