In vitro and in vivo expression of protoporphyrin IX induced by lipophilic 5-aminolevulinic acid derivatives

Ninomiya, Yoshiharu; Itoh, Yoshiyasu; Tajima, S.; Ishibashi, Akira

doi:10.1016/s0923-1811(01)00123-2

Cited by 22 publications

(16 citation statements)

References 16 publications

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“…Because of a low activity of ferrochelatase in tumor cells, the addition of its precursor (5-ALA) will cause endogenous PPIX to accumulate in mitochondria [17,18] . The endogenous PPIX induced by 5-ALA and 5-ALA derivatives in PDT has been well investigated [19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Sonodynamic Antitumor Effect of Protoporphyrin IX Disodium Salt on S180 Solid Tumor

Liu

Wang²,

Wang³

et al. 2007

Chemotherapy

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Background: The sonodynamically induced antitumor effect of protoporphyrin IX (PPIX) disodium salt was studied in mice bearing sarcoma 180 solid tumors. Methods: In order to determine the optimum timing of ultrasound exposure after administration of PPIX, the PPIX concentrations in plasma, skin, muscle and tumor were estimated by measuring the fluorescence intensity of tissue extractions with a fluorescence photometer based on the standard curve. Antitumor effects were estimated by measuring tumor size and calculating the average survival time of tumor-bearing mice after sonodynamic therapy; additionally, the morphological changes of sarcoma 180 cells were evaluated by transmission electron microscope observation in vivo. Results: Our experiments suggested a time of 24 h after the administration of PPIX to be best for ultrasound exposure. At an ultrasound intensity ≧5 W/cm² and a PPIX dose ≧5 mg/kg, a significant synergistic effect of ultrasound combined with PPIX was observed, reducing tumor volume and increasing average animal survival time; this synergistic effect was obviously stronger than ultrasound treatment alone, while PPIX alone showed no significant effect. Transmission electron microscope observation indicated that changes in cell ultrastructure, such as cell membrane destruction, mitochondria swelling and chromatin condensation, were important factors that inhibited tumor growth and even induced cell death. Conclusion: The results implied that the antitumor effect of ultrasound could be enhanced in the presence of PPIX which might be involved in a sonochemical mechanism.

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Section: Introductionmentioning

confidence: 99%

Sonodynamic Antitumor Effect of Protoporphyrin IX Disodium Salt on S180 Solid Tumor

Liu

Wang²,

Wang³

et al. 2007

Chemotherapy

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“…When using ALAhexylester, PpIX formation was 2.5-3.5 times higher for up to 24 h of incubation in cell cultures (8). In vivo, the increase was, however, merely 1.3 (8) and in organ cultures, PpIX formation was not increased with the hexylester (7). Another approach is to target ALA to the mitochondria by increasing the affinity for the mitochondrial membrane, which might be achieved by the use of specific lipids in the formulation (9).…”

Section: Introductionmentioning

confidence: 92%

“…Other parameters, which strongly influence ALA stability, encompass the ALA concentration in a formulation, as well as the viscosity and storage temperature of the formulation (6). Approaches taken to increase the cellular uptake have mainly dealt with increasing the passive diffusion of ALA across the plasma membrane by using more lipophilic ALA prodrugs (7,8). Especially ALA-methylester was effective in a range of clinical trials (1).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Oil-in-Water Emulsions on 5-Aminolevulinic Acid Uptake and Metabolism to PpIX in Cultured MCF-7 Cells

Nielsen

Aemisegger

Burmeister³

et al. 2004

Pharm Res

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“…Tumor selectivity is important to ensure that during treatment the surrounding normal tissue is conserved, and it has been shown that ALA ester derivatives show more tumor selectivity than ALA (6)(7)(8). The application of either ALA or MAL results in the formation of the photosensitizer protoporphyrin IX (PpIX).…”

mentioning

confidence: 99%

A time course investigation of the fluorescence induced by topical application of 5‐aminolevulinic acid and methyl aminolevulinate on normal human skin

Lesar

Ferguson

Moseley

2009

Photoderm Photoimm Photomed

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PpIX fluorescence (following the application of either ALA or MAL) is dependent on duration of application. Following the application of ALA for 1-3 h peak fluorescence was noted at 7 h. Longer duration times (4-6 h) resulted in sustained fluorescence, which peaked at 24 h. MAL-induced fluorescence peaked at 7 h and was significantly decreased by 24 h for all application times. ALA induced fluorescence was shown to be significantly greater than MAL. The findings from this study have shown that potentially it would be more beneficial to apply ALA for shorter periods of time and MAL for longer than current practice.

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In vitro and in vivo expression of protoporphyrin IX induced by lipophilic 5-aminolevulinic acid derivatives

Cited by 22 publications

References 16 publications

Sonodynamic Antitumor Effect of Protoporphyrin IX Disodium Salt on S180 Solid Tumor

Sonodynamic Antitumor Effect of Protoporphyrin IX Disodium Salt on S180 Solid Tumor

Effect of Oil-in-Water Emulsions on 5-Aminolevulinic Acid Uptake and Metabolism to PpIX in Cultured MCF-7 Cells

A time course investigation of the fluorescence induced by topical application of 5‐aminolevulinic acid and methyl aminolevulinate on normal human skin

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