Photodynamic effects induced by meso-tris(pentafluorophenyl)corrole and its cyclodextrin conjugates on cytoskeletal components of HeLa cells (original) (raw)
Related papers
Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer
Cell death & disease, 2014
Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6 J/cm(2), respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosi...
International Journal of Cancer, 1994
The properties of a new photosensitizer, meso-tetrahydroxyphenyl-chlorin (mTHPC), were studied using W9 cells (Chinese-hamster lung fibroblasts). Comparisons were made with 2 other photosensitizers: photofrin II (PII) and meso-tetrahydroxyphenyl-porphyrin (mTHPP). A main advantage of mTHPC is that it has a strong absorption at 652 nm. Maximal cellular uptake of the dye was observed after 24 hr incubation of the cells with the drug. Using a confocal laser-scanning fluorescence microscope, we observed a diffuse distribution of mTHPC in the cytoplasm. Furthermore, the lipophilicity of mTHPC was compared with that of the components of PI1 by means of high-pressure liquid chromatography (HPLC). Absorption and fluorescence spectroscopy indicated that aggregated as well as monomeric mTHPC was bound to the cells. The action spectrum for photo-inactivation of the cells showed that aggregated mTHPC did not contribute significantly to its photosensitizing effects. In the present cellular system, the efficiency of photodynamic therapy (PDT) with mTHPC (cells were irradiated at a wavelength of 652 nm) was higher than with PI1 (irradiation at 630 nm) or with mTHPP (648 nm). The quantum yield for photo-inactivation of cells was smaller for mTHPC than for mTHPP and PII. The addition of I ,3-diphenylisobenzofuran (DPBF) reduced cell inactivation during PDT. Thus, PDT with mTHPC seems to act at least partly via a type4 process. 0 1994 Wiley-Liss, 6~.
Photodynamic effects of a novel pterin derivative on a pancreatic cancer cell line
Biochemical and Biophysical Research Communications, 2005
6-Formylpterin (6FP) has the potential to produce singlet oxygen (1 O 2) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the 1 O 2 generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate 1 O 2 to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable pterin derivatives has the potential for application in PDT.
Photokilling of cultured tumour cells by the porphyrin derivative CF3
We have analysed the photosensitizing properties of the new porphyrin 5-(4-N-(N-2′,6′-dinitro-4′-trifluoromethylphenyl)aminophenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl) porphyrin (CF3) on HeLa cells. The fluorescence and singlet oxygen quantum yield for CF3 were, respectively, φF = 0.032 and φ∆ = 0.25. Cell treatments were done with 5 × 10 -6 M CF3 incorporated into liposome vesicles. Under violet-blue exciting light, the red fluorescence of CF3 was mainly detected in lysosome-like granules. No dark cytotoxicity was observed using high concentration (5 × 10 -6 M) and long incubation time (18 h). Cell cultures treated for 18 h with CF3 and exposed to light (360 < λ < 460 nm; 8 mW/cm 2 ) for 7 min revealed a great amount of apoptotic (75.8%) and detached cells (62%) 8 h later, leading to a cell lethality of 85% (LD 85 ). Apoptosis was identified by chromatin fragmentation and DNA ladder in gel electrophoresis. Necrotic cells were found using 15 min irradiation (LD 96 ) and showed first small and then giant bubbles at the cell surface, with homogeneous nuclear condensation. Incubation with CF3 for 3 h followed by 7 min irradiation (LD38) produced a mitotic arrest 18 h later (mitotic index: 25.1%). Forty-eight hours after this metaphase blockage, cultures showed a great number of apoptotic cells. Taking into account these results, CF3 could be a valuable photosensitizer for the photodynamic therapy of cancer.
Cellular distribution and phototoxicity of Benzoporphyrin derivative and Photofrin
Research in Experimental Medicine, 1999
Photodynamic therapy (PDT) induces cell-membrane damage and alterations in cancer-cell adhesiveness, an important parameter in cancer metastasis. These alterations result from cell sensitivity to photosensitizers and the distribution of photosensitizers in cells. The efficacy of photosensitizers depends on their close proximity to targets and thus on their pharmacokinetics at the cellular level. We studied the cellular distribution of photosensitizers with a confocal microspectrofluorimeter by analysing the fluorescence emitted by benzoporphyrin derivative-monoacid ring A (BPD-MA) and Photofrin relative to their cell sensitivity. Two cancer cell lines of colonic origin, but with different metastatic properties, were used: PROb (progressive) and REGb (regressive). For BPD-MA (1.75 µg/ml), maximal fluorescence intensity (8,300 cts) was reached after 2 h for PROb and after 1 h (4,900 cts) for REGb. For Photofrin (10 µg/ml), maximal fluorescence intensity (467 cts) was reached after 5 h for PROb and after 3 h (404 cts) for REGb. Intracellular studies revealed stronger cytoplasmic than nuclear fluorescence for both BPD and Photofrin. Both of the sensitizers induced a dose-dependent phototoxicity; LD 50 with BPD-MA was 93.3 ng/ml for PROb and 71.1 ng/ml for REGb, under an irradiation of 10 J/cm 2. With Photofrin, LD 50 was 1,270 ng/ml for PROb and 1,200 ng/ml for REGb under an irradiation of 25 J/cm 2. The photosensitizer effect within PROb and REGb cancer cells was assessed by incorporation kinetics and toxicity-phototoxicity tests. The intracellular concentration of the photosensitive agent was one important factor in the effectiveness of PDT, but not the only one contributing to the photodynamic effect. In conclusion, this study showed that there was a clear difference between sensitizer uptake and phototoxicity, even in cancer cells of the same origin. This could induce cell-killing heterogeneity in clinics.
Photodynamic therapy of cancer. Basic principles and applications
Clinical & Translational Oncology, 2008
Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved for clinical treatment of several types of cancer and non-oncological disorders. In PDT, a compound with photosensitising properties (photosensitiser, PS) is selectively accumulated in malignant tissues. The subsequent activation of the PS by visible light, preferentially in the red region of the visible spectrum (λ≥600 nm), where tissues are more permeable to light, generates reactive oxygen species, mainly singlet oxygen (1O2), responsible for cytotoxicity of neoplastic cells and tumour regression. There are three main mechanisms described by which 1O2 contributes to the destruction of tumours by PDT: direct cellular damage, vascular shutdown and activation of immune response against tumour cells. The advantages of PDT over other conventional cancer treatments are its low systemic toxicity and its ability to selectively destroy tumours accessible to light. Therefore, PDT is being used for the treatment of endoscopically accessible tumours such as lung, bladder, gastrointestinal and gynaecological neoplasms, and also in dermatology for the treatment of non-melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic keratosis). Photofrin®, ALA and its ester derivatives are the main compounds used in clinical trials, though newer and more efficient PSs are being evaluated nowadays.
An updated overview on the development of new photosensitizers for anticancer photodynamic therapy
Acta Pharmaceutica Sinica B
Photodynamic therapy (PDT), based on the photoactivation of photosensitizers (PSs), has become a well-studied therapy for cancer. Photofrin ® , belonging to the first generation of PS, is still widely used for the treatment of different kinds of cancers; however, it has several drawbacks that significantly limit its general clinical use. Consequently, there has been extensive research on the design of PS molecules with optimized pharmaceutical properties, with aiming of overcoming the disadvantages of traditional PS, such as poor chemical purity, long half-life, excessive accumulation into the skin, and low attenuation coefficients. The rational design of novel PS with desirable properties has attracted considerable research in the pharmaceutical field. This review presents an overview on the classical photosensitizers and the most significant recent advances in the development of PS with regard to their potential application in oncology.
Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines
PLoS ONE, 2014
Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma.