Enhancement of meta-tetrahydroxyphenylchlorin-sensitized photodynamic treatment on human tumor xenografts using a water-soluble vitamin E analogue, Trolox.
Fiche publication
Date publication
décembre 2000
Journal
International journal of cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BEZDETNAYA-BOLOTINE Lina
Tous les auteurs :
Melnikova VO, Bezdetnaya LN, Brault D, Potapenko AY, Guillemin F
Lien Pubmed
Résumé
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.
Mots clés
Animals, Antineoplastic Agents, therapeutic use, Antioxidants, pharmacology, Chromans, pharmacology, Disease Models, Animal, Drug Interactions, Female, HT29 Cells, Humans, Mesoporphyrins, pharmacokinetics, Mice, Mice, Nude, Neoplasm Transplantation, Neoplasms, Experimental, drug therapy, Oxygen, metabolism, Photochemotherapy, Photosensitizing Agents, pharmacokinetics, Transplantation, Heterologous
Référence
Int. J. Cancer. 2000 Dec;88(5):798-803