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Curcumin as a photosensitizer: Studies on different cell lines
186 for HCP-1 significantly decreased HCP-1 expression. As the result of these phenomena, cancer cellular porphyrin accumulation also decreased. Moreover, the HCP-1 gene transfection derived HCP1 over-expression in HeLa as well as the significant increase of porphyrins accumulation in cancer cells. In addition, the RNAi treatment also restrained cellular proliferation. On the other hand, the up-regulation of HCP-1 expression involved the proliferation increase. Conclusions: HCP-1 transports substrates including porphyin ring. These transportations were suggested to play an important role for a cancer cellular proliferation. doi:10.1016/j.pdpdt.2011.03.213 P007 Model for effects of a broad threshold dose distribution for multisession of photodynamic therapy
Poster Abstracts Sprague—Dawley rats that received a single dose of DMBA (80 mg/kg by gavage). The animals were divided into four groups: G1-control, G2, G3 and G4 will be treated with PDT using an interstitial fiber optic lighting, power 200 mW/cm light dose of 50 J/cm2 , 100 J/cm2 and 150 J/cm2 , respectively. The photosensitizer used was Photogem intraperitoneally and light source used, the laser diode. The animals will be killed 30 h after the lighting and mammary tumors removed. Analyses were made by histopathology and immunohistochemistry. Microscopically, loss of tubulo-alveolar pattern of normal mammary tissue, and large cells with loose chromatin and prominent nucleolus, anisocytosis and anisokaryosis were observed in all groups, an evidence of tumor malignancy. After PDT, coagulation necrosis was established, with an area of necrosis increased from G2 to G4. The antibodies used in immunohistochemistry were Bcl-2, Bax and erb-B2. G1 showed higher proliferation and reduced apoptosis when compared with G3 and G4, so apparently the highest dose of PDT, the lower proliferation and increased cell death.
L.G. Sabino 1 , J.D.V. Filho 1 , J. Ferreira 2 , C. Kurachi 1 , V. Bagnato 1
doi:10.1016/j.pdpdt.2011.03.215
1
University of São Paulo, IFSC, Department of Optics, São Carlos, Brazil 2 University Vale do Paraíba, Institute of Research and Development, Brazil
P009
Photodynamic therapy (PDT) has been used like an alternative local cancer technique. The main limitation of PDT is its limited treatment depth, which causes at bulky tumors the necessity of multiple PDT sessions or the association with surgical procedure. We present a theoretical model to describe the expected effects caused by successive PDT sessions in a bulky tumor. Supposing a partial PDT response of a hypothetical tumor, and considering the existence of a threshold dose distribution within the tumor tissue, represented by a modified Gaussian distribution, we applied a one dimensional light-tissue model. We simulated the tumor response after two PDT applications. Whether there is a continuous distribution of threshold values, a single PDT session does not induce the killing of all cells. The cell fraction left behind promotes a tumor regrowth with different threshold dose distribution. This simple model points out one possible relation between the concept of threshold dose, and the existence of a variety of cells in a tumor mass. We performed an in vitro experiment using Hep-G2 (human liver tumor) cells in a sequence of PDT applications to evaluate the existence of cellular selectivity and to correlate tumor cell variety with threshold distribution. The results showed that the cell death fraction decreases after each PDT application using the same parameters. In addition, such effect may explain why a recurrent cancer lesion shows a potential higher resistance to PDT treatment.
University of Salzburg, Department of Molecular Biology, Salzburg, Austria
doi:10.1016/j.pdpdt.2011.03.214 P008 Influence of photodynamic therapy in mammary carcinogenesis I. Ferreira 1 , C. Grecco 2 , J.D. Vollet-Filho 2 , J. Ferreira 3 , V.S. Bagnato 2 , N.S. Rocha 1 1
UNESP/FMVZ, Department Clínica Veterinária, Botucatu, Brazil 2 USP/IFSC, Department Física e Ciência dos Materiais, São Carlos, Brazil 3 UNIVAP/Instituto de Pesquisa e Desenvolvimento, São Jose dos Campos, Brazil Photodynamic therapy (PDT) is a treatment modality that has been developing rapidly in recent years. The mechanism of PDT causing tissue damage involves a complex interaction between the cell, the photosensitizer (PS) and light. Dosimetry in PDT is important for the safety and effectiveness of the technique. The aim of this study was to correlate the distribution of light with the type of cell death in tumors using underdosing. For that, we used 28
Curcumin as a photosensitizer: Studies on different cell lines T. Verwanger, B. Krammer, E. Bernardinelli
The powdered rhizome of the perennial herb Curcuma longa has been successfully used for centuries in the traditional ayurvedic South East Asian medicine as wound healing and anti-inflammatory remedy. The main component of the extract is a yellowish compound named curcumin (diferuloylmethane). Among its other features, curcumin is known to interact in a peculiar way with visible light acting as a photosensitizer, capable of eliciting destructive intracellular reactions upon light excitation. The main advantage of this particular compound is its extremely low toxicity, since it is part of the daily diet of millions of people in Middle East and South East Asia. Our interest in curcumin was mainly focused on the preliminary determination of the actual efficacy of the compound in the context of a photodynamic treatment, aimed to investigate the potential of curcumin as a photosensitizer, including the determination of its uptake kinetics, its actual phototoxic effects and an eventual malignant/non-malignant selective effect on several cell line models. This study showed a significant phototoxicity elicited by treatment with curcumin in combination with visible light irradiation on the different cell lines tested, in some cases evidencing an interesting selectivity between malignant and non-malignant cell lines. What further emerges from the study is the different behavior of A431 and HaCaT cells upon treatment with irradiated curcumin, leading in the malignant cell line A431 to a significant induction of apoptosis but in the case of HaCaT to the induction of alternative forms of cell death. Such a behavior should be further investigated. doi:10.1016/j.pdpdt.2011.03.216 P010 Study on the interaction between photodynamic therapy and a PI3K pathway inhibitor B. Chen, B. Fateye Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA Introduction: Photodynamic therapy (PDT) induces cell damage and even cell death through the generation of reactive oxygen
Poster Abstracts Sprague—Dawley rats that received a single dose of DMBA (80 mg/kg by gavage). The animals were divided into four groups: G1-control, G2, G3 and G4 will be treated with PDT using an interstitial fiber optic lighting, power 200 mW/cm light dose of 50 J/cm2 , 100 J/cm2 and 150 J/cm2 , respectively. The photosensitizer used was Photogem intraperitoneally and light source used, the laser diode. The animals will be killed 30 h after the lighting and mammary tumors removed. Analyses were made by histopathology and immunohistochemistry. Microscopically, loss of tubulo-alveolar pattern of normal mammary tissue, and large cells with loose chromatin and prominent nucleolus, anisocytosis and anisokaryosis were observed in all groups, an evidence of tumor malignancy. After PDT, coagulation necrosis was established, with an area of necrosis increased from G2 to G4. The antibodies used in immunohistochemistry were Bcl-2, Bax and erb-B2. G1 showed higher proliferation and reduced apoptosis when compared with G3 and G4, so apparently the highest dose of PDT, the lower proliferation and increased cell death.
L.G. Sabino 1 , J.D.V. Filho 1 , J. Ferreira 2 , C. Kurachi 1 , V. Bagnato 1
doi:10.1016/j.pdpdt.2011.03.215
1
University of São Paulo, IFSC, Department of Optics, São Carlos, Brazil 2 University Vale do Paraíba, Institute of Research and Development, Brazil
P009
Photodynamic therapy (PDT) has been used like an alternative local cancer technique. The main limitation of PDT is its limited treatment depth, which causes at bulky tumors the necessity of multiple PDT sessions or the association with surgical procedure. We present a theoretical model to describe the expected effects caused by successive PDT sessions in a bulky tumor. Supposing a partial PDT response of a hypothetical tumor, and considering the existence of a threshold dose distribution within the tumor tissue, represented by a modified Gaussian distribution, we applied a one dimensional light-tissue model. We simulated the tumor response after two PDT applications. Whether there is a continuous distribution of threshold values, a single PDT session does not induce the killing of all cells. The cell fraction left behind promotes a tumor regrowth with different threshold dose distribution. This simple model points out one possible relation between the concept of threshold dose, and the existence of a variety of cells in a tumor mass. We performed an in vitro experiment using Hep-G2 (human liver tumor) cells in a sequence of PDT applications to evaluate the existence of cellular selectivity and to correlate tumor cell variety with threshold distribution. The results showed that the cell death fraction decreases after each PDT application using the same parameters. In addition, such effect may explain why a recurrent cancer lesion shows a potential higher resistance to PDT treatment.
University of Salzburg, Department of Molecular Biology, Salzburg, Austria
doi:10.1016/j.pdpdt.2011.03.214 P008 Influence of photodynamic therapy in mammary carcinogenesis I. Ferreira 1 , C. Grecco 2 , J.D. Vollet-Filho 2 , J. Ferreira 3 , V.S. Bagnato 2 , N.S. Rocha 1 1
UNESP/FMVZ, Department Clínica Veterinária, Botucatu, Brazil 2 USP/IFSC, Department Física e Ciência dos Materiais, São Carlos, Brazil 3 UNIVAP/Instituto de Pesquisa e Desenvolvimento, São Jose dos Campos, Brazil Photodynamic therapy (PDT) is a treatment modality that has been developing rapidly in recent years. The mechanism of PDT causing tissue damage involves a complex interaction between the cell, the photosensitizer (PS) and light. Dosimetry in PDT is important for the safety and effectiveness of the technique. The aim of this study was to correlate the distribution of light with the type of cell death in tumors using underdosing. For that, we used 28
Curcumin as a photosensitizer: Studies on different cell lines T. Verwanger, B. Krammer, E. Bernardinelli
The powdered rhizome of the perennial herb Curcuma longa has been successfully used for centuries in the traditional ayurvedic South East Asian medicine as wound healing and anti-inflammatory remedy. The main component of the extract is a yellowish compound named curcumin (diferuloylmethane). Among its other features, curcumin is known to interact in a peculiar way with visible light acting as a photosensitizer, capable of eliciting destructive intracellular reactions upon light excitation. The main advantage of this particular compound is its extremely low toxicity, since it is part of the daily diet of millions of people in Middle East and South East Asia. Our interest in curcumin was mainly focused on the preliminary determination of the actual efficacy of the compound in the context of a photodynamic treatment, aimed to investigate the potential of curcumin as a photosensitizer, including the determination of its uptake kinetics, its actual phototoxic effects and an eventual malignant/non-malignant selective effect on several cell line models. This study showed a significant phototoxicity elicited by treatment with curcumin in combination with visible light irradiation on the different cell lines tested, in some cases evidencing an interesting selectivity between malignant and non-malignant cell lines. What further emerges from the study is the different behavior of A431 and HaCaT cells upon treatment with irradiated curcumin, leading in the malignant cell line A431 to a significant induction of apoptosis but in the case of HaCaT to the induction of alternative forms of cell death. Such a behavior should be further investigated. doi:10.1016/j.pdpdt.2011.03.216 P010 Study on the interaction between photodynamic therapy and a PI3K pathway inhibitor B. Chen, B. Fateye Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA Introduction: Photodynamic therapy (PDT) induces cell damage and even cell death through the generation of reactive oxygen