In vitro studies on the potential use of 5-aminolaevulinic acid-mediated photodynamic therapy for gynaecological tumours

Rossi, Francesca Maria; Campbell, Donald L.; Pottier, R.; Kennedy, James C.; Dickson, Eva F. Gudgin

doi:10.1038/bjc.1996.452

Cited by 38 publications

(15 citation statements)

References 39 publications

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“…Irradiation with a low energy density (30 J cm -2 ) significantly decreased the cell viability. Other experiments in vitro using different sensitizers and a different setup, yielded a similar cell toxicity (Ma et al, 1994;Jori, 1996;Rossi et al, 1996;Fickweiler et al, 1997). However, ICG concentrations up to 500 µM did not exhibit a dark toxicity.…”

Section: Discussionmentioning

confidence: 84%

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light

et al. 1999

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Summary Despite of the approval of Photofrin® in various countries, chemically defined sensitizers for photodynamic therapy (PDT) are still needed for the absorption of light in the infrared spectrum, which provides a maximal penetration of light into tissue. Therefore, both the efficacy and the mechanism of action of the clinically approved dye indocyanine green (ICG) and laser irradiation were investigated in vitro. For the investigation of phototoxic effects, HT-29 cells were incubated 24 h prior to irradiation by using different concentrations of ICG (10-500 µM). In each experiment, cells were irradiated using a continuous wave (cw)-diode laser (λ ex = 805 nm, 30 J cm -2 , 40 mW cm -2 ). After laser irradiation, cell viability of dark control and of cells incubated with 500 µM ICG was 1.27 ± 0.11 or 0.28 ± 0.05 respectively. Using 100 µM ICG and D 2 O, cell viability was further decreased from 0.46 ± 0.03 (H 2 O) to 0.11 ± 0.01 (D 2 O). Using D 2 O and 100 µM ICG, the concentration of malondialdehyde, a marker of lipid peroxidation, increased from 0.89 ± 0.10 nmol 10 -6 cells to 11.14 ± 0.11 nmol 10 -6 cells. Using 100 µM ICG and laser irradiation sodium azide or histidine (50 mM), quenchers of singlet oxygen reduced the cell killing significantly. In contrast, when using mannitol, a quencher of superoxide anion and hydroxyl radical, cell killing was not inhibited. According to the present results, photoactivated ICG seems to kill colonic cancer cells due to the generation of singlet oxygen and the subsequent formation of lipid peroxides. Therefore, ICG might present a promising photosensitizer for PDT; first clinical results confirm these findings.

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Section: Discussionmentioning

confidence: 84%

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light

et al. 1999

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“…Using confocal fluorescence microscopy, the site of PpIX generation and photodynamic damage has been confirmed to be at the level of the mitochondrion (Rossi et al, 1996). This contrasts with conventional cytotoxic drugs such as MMC, which acts following activation by the bioreductive enzymes DT diaphorase and NADPH cytochrome P450 reductase.…”

Section: Discussionmentioning

confidence: 90%

“…When ALA is used, the mitochondria are important targets (Rossi et al, 1996). This is in contrast to conventional intravesical cytotoxic drugs, such as mitomycin C, which target DNA and the cell nucleus.…”

mentioning

confidence: 97%

Effect of photodynamic therapy in combination with mitomycin C on a mitomycin-resistant bladder cancer cell line

Datta

Allman²,

Loh³

et al. 1997

Br J Cancer

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Summary Photodynamic therapy is a method for treating cancer using drugs activated by light. A new compound, 5-aminolaevulinic acid (ALA), is a precursor of the active photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more transient phototoxicity than previous photosensitizers. Cell survival of ALA-mediated photodynamic therapy was measured in the J82 bladder cancer cell line, along with its mitomycin C-resistant counterpart J82/MMC. This demonstrated that mitomycin resistance is not cross-resistant to photodynamic therapy. There was also a suggestion that the mitomycin-resistant cells were more susceptible to photodynamic therapy than the parent cell line. Photodynamic therapy appeared to enhance the effect of mitomycin C, when mitomycin C was given first. This phenomenon was apparent for both drug-resistant and drug-sensitive cell lines. This suggests a possible role for combined mitomycin C and photodynamic therapy in superficial bladder tumours that have recurred despite intravesical cytotoxic drug treatment.

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“…Using confocal fluorescence microscopy, the site of PpIX generation and photodynamic damage has been confirmed to be at the level of the mitochondrion [8]. In contrast to this, mitomycin-C is activated via a two-electron bioreductive process, via the enzymes DT diaphorase and NADPH cytochrome P450 reductase.…”

Section: Discussionmentioning

confidence: 99%

“…singlet oxygen, which results in damage to cell membrane structures, microvascular ischaemia and tissue necrosis. When ALA is used, the mitochondria are important targets [8], almost certainly because the mitochondria represent the site at which PpIX is locally generated. This is in contrast to conventional intravesical cytotoxic drugs, e.g.…”

Section: Introductionmentioning

confidence: 99%

Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin‐resistant bladder cancer cell‐line model

et al. 2003

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with sequential ALA-mediated PDT and mitomycin C, and with the sequence of treatments reversed. Cell survival was estimated using the tetrazolium assay. The relative mitochondrial density of the two cell lines was estimated using flow cytometry to measure 123 rhodamine fluorescence. RESULTSThe effect of sequential mitomycin C followed by ALA-mediated PDT enhanced the effect of PDT in both cell lines. In J82/MMC this effect was marginally supra-additive. When ALAmediated PDT was administered before mitomycin C, the combined effect was 'sub-additive' . 123Rhodamine fluorescence was > 10 times greater in J82/MMC than J82, suggesting a significantly higher mitochondrial density in the former than the latter.

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In vitro studies on the potential use of 5-aminolaevulinic acid-mediated photodynamic therapy for gynaecological tumours

Cited by 38 publications

References 39 publications

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light

Effect of photodynamic therapy in combination with mitomycin C on a mitomycin-resistant bladder cancer cell line

Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin‐resistant bladder cancer cell‐line model

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