Abstract
Light fractionation, with a long dark interval, significantly increases the response to ALA-PDT in pre-clinical models and in non-melanoma skin cancer. We investigated if this increase in efficacy can be replicated in PAM 212 cells in vitro. The results show a significant decrease in cell survival after light fractionation which is dependent on the PpIX concentration and light dose of the first light fraction. This study supports the hypothesis that an underlying cellular mechanism is involved in the response to light fractionation in which a first light fraction leads to sub-lethally damaged cells that are sensitised to a second light fraction 2 hours later. The current study reveals the in vitro circumstances under which we can investigate the cellular pathways involved.
Notes and references
H. C. de Vijlder, H. J. C. M. Sterenborg, H. A. M. Neumann, D. J. Robinson, E. R. M. de Haas, Light fractionation significantly improves the response of superficial basal cell carcinoma to ALA-PDT: five-year follow-up of a randomized, prospective trial, Acta Dermatol. Venerol., 2012, 92, 641–647.
E. Sotiriou, Z. Apalla, E. Chovarda, C. Goussi, A. Trigoni, D. Ioannides, Single vs. fractionated photodynamic therapy for face and scalp actinic keratoses: a randomized, intraindividual comparison trial with 12-month follow-up, J. Eur. Acad. Dermatol. Venereol., 2012, 26, 36–40.
D. J. Robinson, H. S. de Bruijn, W. M. Star, H. J. C. M. Sterenborg, Dose and timing of the first light fraction in two fold illumination schemes for topical ALA-mediated photodynamic therapy of hairless mouse skin, Photochem. Photobiol., 2003, 77, 319–323.
N. van der Veen, H. L. L. M. van Leengoed, W. M. Star, In vivo fluorescence kinetics and photodynamic therapy using 5-aminolevulinic acid-induced porphyrin: increased damage after multiple irradiations, Br. J. Cancer, 1994, 70, 867–872.
H. S. de Bruijn, N. van der Veen, D. J. Robinson, W. M. Star, Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75 minute interval, Cancer Res., 1999, 59, 901–904.
N. van der Veen, K. M. Hebeda, H. S. de Bruijn, W. M. Star, Photodynamic effectiveness and vasoconstriction in hairless mouse skin after topical 5-aminolevulinic acid and single or two-fold illumination, Photochem. Photobiol., 1999, 70, 921–929.
N. van der Veen, H. S. de Bruijn, W. M. Star, Photobleaching during and re-appearance after photodynamic therapy of topical ALA-induced fluorescence in UVB-treated mouse skin, Int. J. Cancer, 1997, 72, 110–118.
A. Orenstein, G. Kostenich, Z. Malik, The kinetics of protoporphyrin fluorescence during ALA-PDT in human malignant skin tumors, Cancer Lett., 1997, 120, 229–234.
C. af Klintenberg, A. M. K. Enejder, I. Wang, S. Andersson-Engels, S. Svanberg, K. Svandberg, Kinetic fluorescence studies of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation in basal cell carcinomas, J. Photochem. Photobiol., B, 1999, 49, 120–128.
H. S. de Bruijn, B. Kruijt, A. van der Ploeg-van den Heuvel, H. J. C. M. Sterenborg, D. J. Robinson, Increase in protoporphyrin IX after 5-aminolevulinic based photodynamic therapy is due to local resynthesis, Photochem. Photobiol. Sci., 2007, 6, 857–864.
D. J. Robinson, H. S. de Bruijn, J. de Wolf, H. J. C. M. Sterenborg, W. M. Star, Topical 5-aminolevulinic acid-photodynamic therapy of hairless mouse skin using two-fold illumination schemes: PpIX fluorescence kinetics, photobleaching and biological effect, Photochem. Photobiol., 2000, 72, 794–802.
H. S. de Bruijn, A. van der Ploeg–van den Heuvel, H. J. C. M. Sterenborg, D. J. Robinson, Fractionated illumination after topical application of 5-aminolevulinic acid on normal skin of hairless mice: the influence of the dark interval, J. Photochem. Photobiol., B, 2006, 85, 184–190.
T. A. Middelburg, F. van Zaane, H. S. de Bruijn, A. van der Ploeg–van den Heuvel, H. J. C. M. Sterenborg, H. A. M. Neumann, E. R. M. de Haas, D. J. Robinson, Fractionated illumination at low fluence rate photodynamic therapy in mice, Photochem. Photobiol., 2010, 86, 1140–1146.
S. H. Yuspa, P. Hawley-Nelson, B. Koehler, J. R. Stanley, A survey of transformation markers in differentiating epidermal cell lines, Cancer Res., 1980, 40, 4694–4703.
C. Perotti, H. Fukuda, G. DiVenosa, A. J. MacRobert, A. Batlle, A. Casas, Porphyrin synthesis from ALA derivatives for photodynamic therapy, in vitro and in vivo studies, Br. J. Cancer, 2004, 90, 1660–1665.
Z. Ji, G. Yang, V. Vasovic, B. Cunderlikova, Z. Suo, J. M. Nesland, Q. Peng, Subcellular localization pattern of protoporphyrin IX is an important determinant for its photodynamic efficiency of human carcinoma and normal cell lines, J. Photochem. Photobiol., B, 2006, 84, 213–220.
M. J. Niedre, A. J. Secord, M. S. Patterson, B. C. Wilson, In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy, Cancer Res., 2003, 63, 7986–7994.
S. Correa Garcia, A. Casas, C. Perotti, A. Batlle, M. Bermudez Morreti, Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line, Br. J. Cancer, 2003, 89, 173–177.
B. J. Wilson, M. Olivo, G. Singh, Subcellular localization of photofrin and aminolevulinic acid and photodynamic cross-resistance in vitro in radiation-induced fibrosarcoma cells sensitive or resistant to photofrin mediated photodynamic therapy, Photochem. Photobiol., 1997, 65, 166–176.
D. Grebenova, K. Kuzelova, K. Smetana, M. Pluskalova, H. Cajthamlova, I. Marinov, O. Fuchs, J. Soucek, P. Jarolim, Z. Hrkal, Mitochondrial and endoplasmic reticulum stress-induced apoptotic pathways are activated by 5-aminolevulinic acid-based photodynamic therapy in HL60 leukemia cells, J. Photochem. Photobiol., B, 2003, 69, 71–85.
J. Moan, On the diffusion length of singlet oxygen in cells and tissues, J. Photochem. Photobiol., B, 1990, 6, 343–344.
S. K. Bisland, E. A. Goebel, N. S. Hassanali, C. Johnson, B. C. Wilson, Increased expression of mitochondrial benzodiazepine receptors following low-level light treatment facilitates enhanced protoporphyrin IX production in glioma-derived cells in vitro, Lasers Surg. Med., 2007, 39, 678–684.
T. Kriska, W. Korytowski, A. W. Girotti, Role of mitochondrial cardiolipin peroxidation in apoptotic photokilling of 5-aminolevulinate-treated tumor cells, Arch. Biochem. Biophys., 2005, 433, 435–446.
N. L. Oleinick, R. L. Morris, I. Belinchenko, The role of apoptosis in response to photodynamic therapy: what where why and how, Photochem. Photobiol. Sci., 2002, 1, 1–21.
D. Kessel, M. G. Vicente, J. J. Reiners, Initiation of apoptosis and autophagy by photodynamic therapy, Lasers Surg. Med., 2006, 38, 482–488.
E. Buyaert, M. Dewaele, P. Agostinis, Molecular effectors of multiple cell death pathways initiated by photodynamic therapy, Biochim. Biophys. Acta, 2007, 1776, 86–107.
H. T. Ji, L. T. Chen, Y. H. Lin, H. F. Chien, C. H. Chen, 5-ALA mediated photodynamic therapy induces autophagic cell death via the AMP-activated protein kinase, Mol. Cancer, 2010, 9, 91.
I. Coupienne, S. Bontems, M. Dewaele, N. Rubio, Y. Habraken, S. Fulda, P. Agostinis, J. Piette, NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy, Biochem. Pharmacol., 2011, 81, 606–616.
E. R. M. de Haas, H. S. de Bruijn, H. J. C. M. Sterenborg, H. A. M. Neumann, D. J. Robinson, Microscopic distribution of protoporphyrin IX (PpIX) fluorescence in superficial basal cell carcinoma during light fractionated aminolevulinic acid photodynamic therapy, Acta Dermatol. Venerol., 2008, 88, 547–554.
H. S. de Bruijn, E. R. M. de Haas, K. M. Hebeda, A. van der Ploeg–van den Heuvel, H. J. C. M. Sterenborg, H. A. M. Neumann, D. J. Robinson, Light fractionation does not enhance the efficacy of methyl 5-aminolevulinate mediated photodynamic therapy in normal mouse skin, Photochem. Photobiol. Sci., 2007, 6, 1325–1331.
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de Bruijn, H.S., Casas, A.G., Di Venosa, G. et al. Light fractionated ALA-PDT enhances therapeutic efficacy in vitro; the influence of PpIX concentration and illumination parameters. Photochem Photobiol Sci 12, 241–245 (2013). https://doi.org/10.1039/c2pp25287b
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DOI: https://doi.org/10.1039/c2pp25287b