8-Methoxypsoralen potentiates the photocytotoxic effect of Photofrin II towards EMT-6 murine tumor cells

Sousa, Cristina; Mazière, Cécile; Melo, Teresa Sá e; Vincent-Fiquet, O; Rogez, J.C; Santús, René; Mazière, Jean‐Claude

doi:10.1016/s0304-3835(98)00069-x

Cited by 12 publications

(5 citation statements)

References 16 publications

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“…In this context, the potentiation of the porphyrin photodynamic efffect by low 5‐MOP concentration (≤0.5 μ M ) might be explained by an increase in the photosensitizing efficiency of porphyrins or by the induction of an intrinsic phototoxic effect of 5‐MOP under the influence of porphyrin sensitizers. As reported by Sousa et al ( 9 ), at such low UV‐A doses, psorales alone do not kell the cells. However, under these conditions they could produced cytotoxic photoperoxidation products, whose concentration markedly increases in the presenc of porphyrins ( 9 ).…”

Section: Resultssupporting

confidence: 67%

“…As reported by Sousa et al ( 9 ), at such low UV‐A doses, psorales alone do not kell the cells. However, under these conditions they could produced cytotoxic photoperoxidation products, whose concentration markedly increases in the presenc of porphyrins ( 9 ). Although these previous results were obtained with higher concentrations of 5‐MOP (50–100 μ M ), there is no reason to exclude a similar mechanism of action of 5‐MOP during its application in the 0.5–7.0 μ M PP(Arg) 2 were irradiated with red light to avoid any direct photosensitization by 5‐MOP.…”

Section: Resultssupporting

confidence: 67%

“…Another strategy is the development of combination therapies associating PDT with another treatment allowing the use of lower photosensitizer or light doses (or both). In this regard, it was demonstrated that the combination of Photofrin with 8‐methoxypsoralen, a furocoumarin used in the psoralens + ultraviolet‐A (UV‐A) (PUVA) photochemotherapy ( 8 ), potentiates the phototoxicity of Photofrin toward murine tumor cells ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen^†;

Bugaj

Morllére

Santús

et al. 2004

Photochem & Photobiology

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The phototoxicity of two new porphyrin photosensitizers, diarginine diprotoporphyrinate (PP(Arg)2) and N,N‐diphenylalanyl protoporphyrin (PP(Phe)2), and the synergistic effect of 5‐methaoxyposralen (5‐MOP) have been studied in comparison with that of protoporphyrin IX (PPIX). Under ultraviolet A (UV‐A) irradiation (λ= 365 nm), the phototoxicity of the porphyrins toward cultured human fibroblasts and keratino‐cytes decerases in the order: PPIX > PP(Arg)2 > PP(Phe)2. A synergistic efect of 5‐MOP on the phototoxicity of PPIX, PP(Arg)2 and PP(Phe)2 has been observed. The combination of PPIX, PP(Arg)2 and PP(Phe)2 with 0.1–0.5 μM 5‐MOP significantly potentiates the phototoxicity of the three porphyrins. The most effective potentiation was observed with the water‐soluble PP(Arg)2 and 5‐MOP concentrations lowere than 0.75 μM. Above this 5‐MOP concnetration this potentiation is abolished. The intracellular concentration of PPIX and PP(Phe)2 is independent of the presence of 5‐MOP. On the other hand, the intracellular contnet of PP(Arg)2 is decerased in concentration‐dependent manner by the psoralen. Illumination with red light, not absorbed by 5‐MOP, leads to a weak potentiation of the PP(Arg)2 phototoxic effect in the presence of 5‐MOP, suggesting that dark interaction of 5‐MOP with cell membranes aggravated by porphyrin photosensitization is involved in the observed phenomena. The results are tentatively explained by differences in hydrophobicity and molecular structure of the examined photosensitizers. PPIX, which is barely soluble in water, has a significantly higher affinity for cell membranes and simultaneously exerts a stronger phototoxic effect than PP(Arg)2 whose solubility in water is high. On the other hand, the weak phototoxicity of PP(Phe)2 could be explained by the steric hindrance brought by the phenylalanyl substituents on the pyrrole ring. The loss in the PP(Arg)2 cell content probably explains the inhibition of the synergistic effect of 5‐MOP on the PP(Arg)2 phototoxicity at high 5‐MOP concentration. This study suggests that PP(Arg)2 in combinatin with 5‐MOP might reveal a strong phototoxic effect when applied to skin cancer treatment.

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Section: Resultssupporting

confidence: 67%

Section: Resultssupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen^†;

Bugaj

Morllére

Santús

et al. 2004

Photochem & Photobiology

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“…As reported by Sousa et al (9), at such low UV-A doses, psoralens alone do not kill the cells. However, under these conditions they could produce cytotoxic photoperoxidation products, whose concentration markedly increases in the presence of porphyrins (9). Although these previous Figure 5.…”

Section: Resultsmentioning

confidence: 96%

“…Another strategy is the development of combination therapies associating PDT with another treatment allowing the use of lower photosensitizer or light doses (or both). In this regard, it was demonstrated that the combination of Photofrin with 8-methoxypsoralen, a furocoumarin used in the psoralens + ultraviolet-A (UV-A) (PUVA) photochemotherapy (8), potentiates the phototoxicity of Photofrin toward murine tumor cells (9). During the past decade, a new group of photosensitizers has been developed, which are amino acid derivatives of porphyrins (10) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Phototoxicity of Protoporphyrin IX, Diarginine Diprotoporphyrinate and N,N-Diphenylalanyl Protoporphyrin Toward Human Fibroblasts and Keratinocytes In Vitro: Effect of 5-Methoxypsoralen ¶

Bugaj

Morlière

Santús

et al. 2004

Photochem Photobiol

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The phototoxicity of two new porphyrin photosensitizers, diarginine diprotoporphyrinate (PP(Arg)2) and N,N-diphenylalanyl protoporphyrin (PP(Phe)2), and the synergistic effect of 5-methoxyposralen (5-MOP) have been studied in comparison with that of protoporphyrin IX (PPIX). Under ultraviolet-A (UV-A) irradiation (h = 365 nm), the phototoxicity of the porphyrins toward cultured human fibroblasts and keratinocytes decreases in the order: PPIX > PP(Arg)z > PP(Phe)> A synergistic effect of 5-MOP on the phototoxicity of PPIX, PP(Arg), and PP(Phe)2 has been observed. The combination of PPIX, PP(Arg)2 and PP(Phe)2 with 0.1-0.5 pA4 5-MOP significantly potentiates the phototoxicity of the three porphyrins. The most effective potentiation was observed with the water-soluble PP(Arg)z and 5-MOP concentrations lower than 0.75 pM. Above this 5-MOP concentration this potentiation is abolished. The intracellular concentration of PPIX and PP(Phe)2 is independent of the presence of 5-MOP. On the other hand, the intracellular content of PP(Arg)2 is decreased in a concentration-dependent manner by the psoralen. Illumination with red light, not absorbed by 5-MOP, leads to a weak potentiation of the PP(Arg), phototoxic effect in the presence of !?-MOP, suggesting that dark interaction of 5-MOP with cell membranes aggravated by porphyrin photosensitization is involved in the observed phenomena. The results are tentatively explained by differences in hydrophobicity and molecular structures of the examined photosensitizers. PPIX, which is barely soluble in water, Abbreviations: DMEM, Dulbecco's modified minimum essential medium;EMEM, Eagle's minimum essential medium with Earle's salts; FCS, fetal calf serum; HBSS, Hank's buffered saline solution: ID,,, dose inhibiting 50% of membrane integrity; 5-MOP, 5-methoxypsoralen; NR, neutral red; PBS, phosphate-buffered saline solution; PDT, photodynamic therapy; PP(Arg),, diarginine diprotoporphyrinate; PPIX, protoporphyrin IX, PP(Phe),, N,N-diphenylalanyl protoporphyrin; PUVA, psoralens + ultraviolet-A, UV-A, ultraviolet-A. 0 2004 American Society for Photobiology 003 1 -8655/04 $5.00+0.00 has a significantly higher affinity for cell membranes and simultaneously exerts a stronger phototoxic effect than PP(Arg)2 whose solubility in water is high. On the other hand, the weak phototoxicity of PP(Phe)2 could be explained by the steric hindrance brought by the phenylalanyl substituents on the pyrrole ring. The loss in the PP(ArgI2 cell content probably explains the inhibition of the synergistic effect of 5-MOP on the PP(Arg)t phototoxicity at high 5-MOP concentration. This study suggests that PP(Arg), in combination with 5-MOP might reveal a strong phototoxic effect when applied to skin cancer treatment.

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Peripherally Metallated Porphyrins: the First Examples of meso‐η¹‐Palladio(II) and ‐Platinio(II) Complexes with Chelating Diamine Ligands

Hartnell

Arnold

2004

Eur J Inorg Chem

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The oxidative addition of bis(dibenzylideneacetone)platinum(0) to meso‐bromo‐5,15‐diarylporphyrins in the presence of PPh3 has been shown to be an effective way of synthesising η1‐organoplatinum porphyrins in high yields. This methodology has been extended to synthesise various palladio‐ and platinioporphyrins that utilise bidentate nitrogen donor ligands [N,N,N′,N′‐tetramethylethylenediamine (tmeda) and 2,2′‐bipyridyl (bpy)] in order to enforce a cis configuration at the metal centre. The products were characterised by multinuclear NMR and UV‐Vis spectroscopy as well as fast‐atom bombardment and high‐resolution electrospray ionisation mass spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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8-Methoxypsoralen potentiates the photocytotoxic effect of Photofrin II towards EMT-6 murine tumor cells

Cited by 12 publications

References 16 publications

Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen^†;

Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen^†;

Phototoxicity of Protoporphyrin IX, Diarginine Diprotoporphyrinate and N,N-Diphenylalanyl Protoporphyrin Toward Human Fibroblasts and Keratinocytes In Vitro: Effect of 5-Methoxypsoralen ¶

Peripherally Metallated Porphyrins: the First Examples of meso‐η¹‐Palladio(II) and ‐Platinio(II) Complexes with Chelating Diamine Ligands

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8-Methoxypsoralen potentiates the photocytotoxic effect of Photofrin II towards EMT-6 murine tumor cells

Cited by 12 publications

References 16 publications

Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen†;

Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen†;

Phototoxicity of Protoporphyrin IX, Diarginine Diprotoporphyrinate and N,N-Diphenylalanyl Protoporphyrin Toward Human Fibroblasts and Keratinocytes In Vitro: Effect of 5-Methoxypsoralen ¶

Peripherally Metallated Porphyrins: the First Examples of meso‐η1‐Palladio(II) and ‐Platinio(II) Complexes with Chelating Diamine Ligands

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Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen^†;

Phototoxicity of Protoporphhyrin IX, Diarginine Diprotoporphyrinate and N,N‐Deiphenylalanyl Protoporphyrin Toward Human Fibroblasts and ketratinocytes In vitro: Effect of 5‐Methoxypsoralen^†;

Peripherally Metallated Porphyrins: the First Examples of meso‐η¹‐Palladio(II) and ‐Platinio(II) Complexes with Chelating Diamine Ligands