Photodiagnosis and Photodynamic Therapy
Volume 2, Issue 1 , Pages 1-23 , March 2005

Mechanisms in photodynamic therapy: part two—cellular signaling, cell metabolism and modes of cell death

  • Ana P. Castano

      Affiliations

    • BAR314B, Wellman Center for Photomedicine, Massachusetts General Hospital, 50 Blossom Street, Bartlett 3, Boston, MA 02114, USA
    • Department of Dermatology, Harvard Medical School, USA
    • ,
  • Tatiana N. Demidova

      Affiliations

    • BAR314B, Wellman Center for Photomedicine, Massachusetts General Hospital, 50 Blossom Street, Bartlett 3, Boston, MA 02114, USA
    • Department of Cellular, Molecular and Developmental Biology, Tufts University, USA
    • ,
  • Michael R. Hamblin, PhD

      Affiliations

    • BAR314B, Wellman Center for Photomedicine, Massachusetts General Hospital, 50 Blossom Street, Bartlett 3, Boston, MA 02114, USA
    • Department of Dermatology, Harvard Medical School, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 617 726 6182; fax: +1 617 726 8566.

References 

  1. Samali A, Gorman AM, Cotter TG. Apoptosis—the story so far …. Experimentia. 1996;52:933–941
  2. Dixon SC, Soriano BJ, Lush RM, Borner MM, Figg WD. Apoptosis: its role in the development of malignancies and its potential as a novel therapeutic target. Ann Pharmacother. 1997;31:76–82
  3. Oleinick NL, Morris RL, Belichenko I. The role of apoptosis in response to photodynamic therapy: what, where, why, and how. Photochem Photobiol Sci. 2002;1:1–21
  4. McCarthy JV. Apoptosis and development. Essays Biochem. 2003;39:11–24
  5. Hildeman DA. Regulation of T-cell apoptosis by reactive oxygen species. Free Radic Biol Med. 2004;36:1496–1504
  6. Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. Oncol Rep. 2003;10:1663–1682
  7. Pruschy M, Rocha S, Zaugg K, et al. Key targets for the execution of radiation-induced tumor cell apoptosis: the role of p53 and caspases. Int J Radiat Oncol Biol Phys. 2001;49:561–567
  8. Villard J. Transcription regulation and human diseases. Swiss Med Wkly. 2004;134:571–579
  9. Castano AP, Demidova TN, Hamblin MR. Mechanism in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther. 2004;1:279–293
  10. Wilson BC, Olivo M, Singh G. 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
  11. Penning LC, Rasch MH, Ben-Hur E, et al. A role for the transient increase of cytoplasmic free calcium in cell rescue after photodynamic treatment. Biochim Biophys Acta. 1992;1107:255–260
  12. Joshi PG, Joshi K, Mishra S, Joshi NB. Ca2+ influx induced by photodynamic action in human cerebral glioma (U-87 MG) cells: possible involvement of a calcium channel. Photochem Photobiol. 1994;60:244–248
  13. Hubmer A, Hermann A, Uberriegler K, Krammer B. Role of calcium in photodynamically induced cell damage of human fibroblasts. Photochem Photobiol. 1996;64:211–215
  14. Cui ZJ, Habara Y, Wang DY, Kanno T. A novel aspect of photodynamic action: induction of recurrent spikes in cytosolic calcium concentration. Photochem Photobiol. 1997;65:382–386
  15. Specht KG, Rodgers MA. Plasma membrane depolarization and calcium influx during cell injury by photodynamic action. Biochim Biophys Acta. 1991;1070:60–68
  16. Ding X, Xu Q, Liu F, et al. Hematoporphyrin monomethyl ether photodynamic damage on HeLa cells by means of reactive oxygen species production and cytosolic free calcium concentration elevation. Cancer Lett. 2004;216:43–54
  17. Grebenova D, Kuzelova K, Smetana K, et al. 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
  18. Granville DJ, Ruehlmann DO, Choy JC, et al. Bcl-2 increases emptying of endoplasmic reticulum Ca2+ stores during photodynamic therapy-induced apoptosis. Cell Calcium. 2001;30:343–350
  19. Ruck A, Heckelsmiller K, Kaufmann R, Grossman N, Haseroth E, Akgun N. Light-induced apoptosis involves a defined sequence of cytoplasmic and nuclear calcium release in AlPcS4-photosensitized rat bladder RR 1022 epithelial cells. Photochem Photobiol. 2000;72:210–216
  20. Berridge MJ, Irvine RF. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984;312:315–321
  21. Berridge MJ. Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem. 1987;56:159–193
  22. Santini MP, Talora C, Seki T, Bolgan L, Dotto GP. Cross talk among calcineurin, Sp1/Sp3, and NFAT in control of p21(WAF1/CIP1) expression in keratinocyte differentiation. Proc Natl Acad Sci USA. 2001;98:9575–9580
  23. Penning LC, Keirse MJ, Van Steveninck J, Dubbelman TM. Ca(2+)-mediated prostaglandin E2 induction reduces haematoporphyrin-derivative-induced cytotoxicity of T24 human bladder transitional carcinoma cells in vitro. Biochem J. 1993;292(Pt. 1):237–240
  24. Agarwal ML, Larkin HE, Zaidi SI, Mukhtar H, Oleinick NL. Phospholipase activation triggers apoptosis in photosensitized mouse lymphoma cells. Cancer Res. 1993;53:5897–5902
  25. Henderson BW, Donovan JM. Release of prostaglandin E2 from cells by photodynamic treatment in vitro. Cancer Res. 1989;49:6896–6900
  26. Henderson BW, Owczarczak B, Sweeney J, Gessner T. Effects of photodynamic treatment of platelets or endothelial cells in vitro on platelet aggregation. Photochem Photobiol. 1992;56:513–521
  27. al-Laith M, Matthews EK, Cui ZJ. Photodynamic drug action on isolated rat pancreatic acini. Mobilization of arachidonic acid and prostaglandin production. Biochem Pharmacol. 1993;46:567–573
  28. Foultier MT, Patrice T, Yactayo S, Lajat Y, Resche F. Photodynamic treatment of normal endothelial cells or glioma cells in vitro. Surg Neurol. 1992;37:83–88
  29. Fingar VH, Wieman TJ, Doak KW. Role of thromboxane and prostacyclin release on photodynamic therapy-induced tumor destruction. Cancer Res. 1990;50:2599–2603
  30. Fingar VH, Siegel KA, Wieman TJ, Doak KW. The effects of thromboxane inhibitors on the microvascular and tumor response to photodynamic therapy. Photochem Photobiol. 1993;58:393–399
  31. Ferrario A, Von Tiehl K, Wong S, Luna M, Gomer CJ. Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. Cancer Res. 2002;62:3956–3961
  32. Bektas M, Spiegel S. Glycosphingolipids and cell death. Glycoconj J. 2004;20:39–47
  33. Yang J, Yu Y, Sun S, Duerksen-Hughes PJ. Ceramide and other sphingolipids in cellular responses. Cell Biochem Biophys. 2004;40:323–350
  34. Separovic D, Mann KJ, Oleinick NL. Association of ceramide accumulation with photodynamic treatment-induced cell death. Photochem Photobiol. 1998;68:101–109
  35. Dolgachev V, Farooqui MS, Kulaeva OI, et al. De novo ceramide accumulation due to inhibition of its conversion to complex sphingolipids in apoptotic photosensitized cells. J Biol Chem. 2004;279:23238–23249
  36. Separovic D, Pink JJ, Oleinick NA, et al. Niemann-Pick human lymphoblasts are resistant to phthalocyanine 4-photodynamic therapy-induced apoptosis. Biochem Biophys Res Commun. 1999;258:506–512
  37. Chiu SM, Davis TW, Meyers M, Ahmad N, Mukhtar H, Separovic D. Phthalocyanine 4-photodynamic therapy induces ceramide generation and apoptosis in acid sphingomyelinase-deficient mouse embryonic fibroblasts. Int J Oncol. 2000;16:423–427
  38. Murray AW. MAP kinases in meiosis. Cell. 1998;92:157–159
  39. Schaeffer HJ, Weber MJ. Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol. 1999;19:2435–2444
  40. Tao J, Sanghera JS, Pelech SL, Wong G, Levy JG. Stimulation of stress-activated protein kinase and p38 HOG1 kinase in murine keratinocytes following photodynamic therapy with benzoporphyrin derivative. J Biol Chem. 1996;271:27107–27115
  41. Xue L, He J, Oleinick NL. Promotion of photodynamic therapy-induced apoptosis by stress kinases. Cell Death Differ. 1999;6:855–864
  42. Hendrickx N, Volanti C, Moens U, et al. Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. J Biol Chem. 2003;278:52231–52239
  43. Tong Z, Singh G, Rainbow AJ. Sustained activation of the extracellular signal-regulated kinase pathway protects cells from photofrin-mediated photodynamic therapy. Cancer Res. 2002;62:5528–5535
  44. Klotz LO, Fritsch C, Briviba K, Tsacmacidis N, Schliess F, Sies H. Activation of JNK and p38 but not ERK MAP kinases in human skin cells by 5-aminolevulinate-photodynamic therapy. Cancer Res. 1998;58:4297–4300
  45. Castillo L, Etienne-Grimaldi MC, Fischel JL, Formento P, Magne N, Milano G. Pharmacological background of EGFR targeting. Ann Oncol. 2004;15:1007–1012
  46. Wong TW, Tracy E, Oseroff AR, Baumann H. Photodynamic therapy mediates immediate loss of cellular responsiveness to cytokines and growth factors. Cancer Res. 2003;63:3812–3818
  47. Ahmad N, Kalka K, Mukhtar H. In vitro and in vivo inhibition of epidermal growth factor receptor-tyrosine kinase pathway by photodynamic therapy. Oncogene. 2001;20:2314–2317
  48. Nakano H. Signaling crosstalk between NF-kappaB and JNK. Trends Immunol. 2004;25:402–405
  49. Holbrook NJ, Liu Y, Fornace AJ. Signaling events controlling the molecular response to genotoxic stress. EXS. 1996;77:273–288
  50. Assefa Z, Vantieghem A, Declercq W, et al. The activation of the c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling pathways protects HeLa cells from apoptosis following photodynamic therapy with hypericin. J Biol Chem. 1999;274:8788–8796
  51. Scheid MP, Woodgett JR. Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett. 2003;546:108–112
  52. Sen P, Mukherjee S, Ray D, Raha S. Involvement of the Akt/PKB signaling pathway with disease processes. Mol Cell Biochem. 2003;253:241–246
  53. Zhuang S, Kochevar IE. Singlet oxygen-induced activation of Akt/protein kinase B is independent of growth factor receptors. Photochem Photobiol. 2003;78:361–371
  54. Schieke SM, von Montfort C, Buchczyk DP, et al. Singlet oxygen-induced attenuation of growth factor signaling: possible role of ceramides. Free Radic Res. 2004;38:729–737
  55. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol. 2002;4:E131–E136
  56. Luna MC, Wong S, Gomer CJ. Photodynamic therapy mediated induction of early response genes. Cancer Res. 1994;54:1374–1380
  57. Kick G, Messer G, Plewig G, Kind P, Goetz AE. Strong and prolonged induction of c-jun and c-fos proto-oncogenes by photodynamic therapy. Br J Cancer. 1996;74:30–36
  58. Kick G, Messer G, Goetz A, Plewig G, Kind P. Photodynamic therapy induces expression of interleukin 6 by activation of AP-1 but not NF-kappa B DNA binding. Cancer Res. 1995;55:2373–2379
  59. Ryter SW, Gomer CJ. Nuclear factor kappa B binding activity in mouse L1210 cells following photofrin II-mediated photosensitization. Photochem Photobiol. 1993;58:753–756
  60. Piret B, Legrand-Poels S, Sappey C, Piette J. NF-kappa B transcription factor and human immunodeficiency virus type 1 (HIV-1) activation by methylene blue photosensitization. Eur J Biochem. 1995;228:447–455
  61. Legrand-Poels S, Bours V, Piret B, et al. Transcription factor NF-kappa B is activated by photosensitization generating oxidative DNA damages. J Biol Chem. 1995;270:6925–6934
  62. Matroule JY, Bonizzi G, Morliere P, et al. Pyropheophorbide-a methyl ester-mediated photosensitization activates transcription factor NF-kappaB through the interleukin-1 receptor-dependent signaling pathway. J Biol Chem. 1999;274:2988–3000
  63. Volanti C, Matroule JY, Piette J. Involvement of oxidative stress in NF-kappaB activation in endothelial cells treated by photodynamic therapy. Photochem Photobiol. 2002;75:36–45
  64. Kaltschmidt B, Kaltschmidt C, Hofmann TG, Hehner SP, Droge W, Schmitz ML. The pro- or anti-apoptotic function of NF-kappaB is determined by the nature of the apoptotic stimulus. Eur J Biochem. 2000;267:3828–3835
  65. Kucharczak J, Simmons MJ, Fan Y, Gelinas C. To be, or not to be: NF-kappaB is the answer—role of Rel/NF-kappaB in the regulation of apoptosis. Oncogene. 2003;22:8961–8982
  66. Granville DJ, Carthy CM, Jiang H, et al. Nuclear factor-kappaB activation by the photochemotherapeutic agent verteporfin. Blood. 2000;95:256–262
  67. Bracken AP, Ciro M, Cocito A, Helin K. E2F target genes: unraveling the biology. Trends Biochem. Sci. 2004;29:409–417
  68. Stevens C, La Thangue NB. E2F and cell cycle control: a double-edged sword. Arch Biochem Biophys. 2003;412:157–169
  69. Ahmad N, Feyes DK, Agarwal R, Mukhtar H. Photodynamic therapy results in induction of WAF1/CIP1/P21 leading to cell cycle arrest and apoptosis. Proc Natl Acad Sci USA. 1998;95:6977–6982
  70. Ahmad N, Gupta S, Mukhtar H. Involvement of retinoblastoma (Rb) and E2F transcription factors during photodynamic therapy of human epidermoid carcinoma cells A431. Oncogene. 1999;18:1891–1896
  71. Colussi VC, Feyes DK, Mulvihill JW, et al. Phthalocyanine 4 (Pc4) photodynamic therapy of human OVCAR-3 tumor xenografts. Photochem Photobiol. 1999;69:236–241
  72. Whitacre CM, Feyes DK, Satoh T, et al. Photodynamic therapy with the phthalocyanine photosensitizer Pc4 of SW480 human colon cancer xenografts in athymic mice. Clin Cancer Res. 2000;6:2021–2027
  73. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110:673–687
  74. Patel KD, Cuvelier SL, Wiehler S. Selectins: critical mediators of leukocyte recruitment. Semin Immunol. 2002;14:73–81
  75. Cavallaro U, Christofori G. Multitasking in tumor progression: signaling functions of cell adhesion molecules. Ann N Y Acad Sci. 2004;1014:58–66
  76. George SJ, Dwivedi A. MMPs, cadherins, and cell proliferation. Trends Cardiovasc Med. 2004;14:100–105
  77. Ball DJ, Mayhew S, Vernon DI, Griffin M, Brown SB. Decreased efficiency of trypsinization of cells following photodynamic therapy: evaluation of a role for tissue transglutaminase. Photochem Photobiol. 2001;73:47–53
  78. Runnels JM, Chen N, Ortel B, Kato D, Hasan T. BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and beta1 integrin expression in ovarian cancer cells. Br J Cancer. 1999;80:946–953
  79. Rousset N, Vonarx V, Eleouet S, et al. Effects of photodynamic therapy on adhesion molecules and metastasis. J Photochem Photobiol B. 1999;52:65–73
  80. Vonarx V, Foultier MT, Xavier de Brito L, Anasagasti L, Morlet L, Patrice T. Photodynamic therapy decreases cancer colonic cell adhesiveness and metastatic potential. Res Exp Med (Berl). 1995;195:101–116
  81. Uzdensky AB, Juzeniene A, Kolpakova E, Hjortland GO, Juzenas P, Moan J. Photosensitization with protoporphyrin IX inhibits attachment of cancer cells to a substratum. Biochem Biophys Res Commun. 2004;322:452–457
  82. Uzdensky A, Juzeniene A, Ma LW, Moan J. Photodynamic inhibition of enzymatic detachment of human cancer cells from a substratum. Biochim Biophys Acta. 2004;1670:1–11
  83. Momma T, Hamblin MR, Wu HC, Hasan T. Photodynamic therapy of orthotopic prostate cancer with benzoporphyrin derivative: local control and distant metastasis. Cancer Res. 1998;58:5425–5431
  84. de Vree WJ, Fontijne-Dorsman AN, Koster JF, Sluiter W. Photodynamic treatment of human endothelial cells promotes the adherence of neutrophils in vitro. Br J Cancer. 1996;73:1335–1340
  85. Fungaloi P, Statius van Eps R, Wu YP, et al. Platelet adhesion to photodynamic therapy-treated extracellular matrix proteins. Photochem Photobiol. 2002;75:412–417
  86. Volanti C, Gloire G, Vanderplasschen A, Jacobs N, Habraken Y, Piette J. Downregulation of ICAM-1 and VCAM-1 expression in endothelial cells treated by photodynamic therapy. Oncogene. 2004;23:8649–8658
  87. Evans S, Matthews W, Perry R, Fraker D, Norton J, Pass HI. Effect of photodynamic therapy on tumor necrosis factor production by murine macrophages. J Natl Cancer Inst. 1990;82:34–39
  88. Anderson C, Hrabovsky S, McKinley Y, et al. Phthalocyanine photodynamic therapy: disparate effects of pharmacologic inhibitors on cutaneous photosensitivity and on tumor regression. Photochem Photobiol. 1997;65:895–901
  89. Coutier S, Bezdetnaya L, Marchal S, et al. Foscan (mTHPC) photosensitized macrophage activation: enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-alpha-mediated cytolytic activity. Br J Cancer. 1999;81:37–42
  90. Herman S, Kalechman Y, Gafter U, Sredni B, Malik Z. Photofrin II induces cytokine secretion by mouse spleen cells and human peripheral mononuclear cells. Immunopharmacology. 1996;31:195–204
  91. Usuda J, Okunaka T, Furukawa K, et al. Increased cytotoxic effects of photodynamic therapy in IL-6 gene transfected cells via enhanced apoptosis. Int J Cancer. 2001;93:475–480
  92. Gollnick SO, Lee BY, Vaughan L, Owczarczak B, Henderson BW. Activation of the IL-10 gene promoter following photodynamic therapy of murine keratinocytes. Photochem Photobiol. 2001;73:170–177
  93. Gollnick SO, Evans SS, Baumann H, et al. Role of cytokines in photodynamic therapy-induced local and systemic inflammation. Br J Cancer. 2003;88:1772–1779
  94. Cecic I, Parkins CS, Korbelik M. Induction of systemic neutrophil response in mice by photodynamic therapy of solid tumors. Photochem Photobiol. 2001;74:712–720
  95. Sun J, Cecic I, Parkins CS, Korbelik M. Neutrophils as inflammatory and immune effectors in photodynamic therapy-treated mouse SCCVII tumours. Photochem Photobiol Sci. 2002;1:690–695
  96. Gollnick SO, Liu X, Owczarczak B, Musser DA, Henderson BW. Altered expression of interleukin 6 and interleukin 10 as a result of photodynamic therapy in vivo. Cancer Res. 1997;57:3904–3909
  97. Cecic I, Korbelik M. Mediators of peripheral blood neutrophilia induced by photodynamic therapy of solid tumors. Cancer Lett. 2002;183:43–51
  98. Nseyo UO, Whalen RK, Duncan MR, Berman B, Lundahl SL. Urinary cytokines following photodynamic therapy for bladder cancer. A preliminary report. Urology. 1990;36:167–171
  99. Yom SS, Busch TM, Friedberg JS, et al. Elevated serum cytokine levels in mesothelioma patients who have undergone pleurectomy or extrapleural pneumonectomy and adjuvant intraoperative photodynamic therapy. Photochem Photobiol. 2003;78:75–81
  100. Morimoto RI. Cells in stress: transcriptional activation of heat shock genes. Science. 1993;259:1409–1410
  101. Gomer CJ, Ferrario A, Rucker N, Wong S, Lee AS. Glucose regulated protein induction and cellular resistance to oxidative stress mediated by porphyrin photosensitization. Cancer Res. 1991;51:6574–6579
  102. Gomer CJ, Ryter SW, Ferrario A, Rucker N, Wong S, Fisher AM. Photodynamic therapy-mediated oxidative stress can induce expression of heat shock proteins. Cancer Res. 1996;56:2355–2360
  103. Luna MC, Ferrario A, Wong S, Fisher AM, Gomer CJ. Photodynamic therapy-mediated oxidative stress as a molecular switch for the temporal expression of genes ligated to the human heat shock promoter. Cancer Res. 2000;60:1637–1644
  104. Luna MC, Chen X, Wong S, et al. Enhanced photodynamic therapy efficacy with inducible suicide gene therapy controlled by the grp promoter. Cancer Res. 2002;62:1458–1461
  105. Hanlon JG, Adams K, Rainbow AJ, Gupta RS, Singh G. Induction of Hsp60 by Photofrin-mediated photodynamic therapy. J Photochem Photobiol B. 2001;64:55–61
  106. Wang HP, Hanlon JG, Rainbow AJ, Espiritu M, Singh G. Up-regulation of Hsp27 plays a role in the resistance of human colon carcinoma HT29 cells to photooxidative stress. Photochem Photobiol. 2002;76:98–104
  107. Mitra S, Goren EM, Frelinger JG, Foster TH. Activation of heat shock protein 70 promoter with meso-tetrahydroxyphenyl chlorine photodynamic therapy reported by green fluorescent protein in vitro and in vivo. Photochem Photobiol. 2003;78:615–622
  108. Jalili A, Makowski M, Switaj T, et al. Effective photoimmunotherapy of murine colon carcinoma induced by the combination of photodynamic therapy and dendritic cells. Clin Cancer Res. 2004;10:4498–4508
  109. Alam J, Den Z. Distal AP-1 binding sites mediate basal level enhancement and TPA induction of the mouse heme oxygenase-1 gene. J Biol Chem. 1992;267:21894–21900
  110. Gomer CJ, Luna M, Ferrario A, Rucker N. Increased transcription and translation of heme oxygenase in Chinese hamster fibroblasts following photodynamic stress or Photofrin II incubation. Photochem Photobiol. 1991;53:275–279
  111. Bressoud D, Jomini V, Tyrrell RM. Dark induction of haem oxygenase messenger RNA by haematoporphyrin derivative and zinc phthalocyanine; agents for photodynamic therapy. J Photochem Photobiol B. 1992;14:311–318
  112. Lin F, Girotti AW. Hyperresistance of leukemia cells to photodynamic inactivation after long-term exposure to hemin. Cancer Res. 1996;56:4636–4643
  113. Das H, Koizumi T, Sugimoto T, et al. Induction of apoptosis and manganese super-oxide dismutase gene by photodynamic therapy in cervical carcinoma cell lines. Int J Clin Oncol. 2000;5:97–103
  114. Golab J, Nowis D, Skrzycki M, et al. Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol. A superoxide dismutase inhibitor. J Biol Chem. 2003;278:407–414
  115. Lu WD, Atkins WM. A novel antioxidant role for ligandin behavior of glutathione S-transferases: attenuation of the photodynamic effects of hypericin. Biochemistry. 2004;43:12761–12769
  116. Semenza GL. Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology. 2004;19:176–182
  117. Mazure NM, Brahimi-Horn MC, Berta MA, et al. HIF-1: master and commander of the hypoxic world. A pharmacological approach to its regulation by siRNAs. Biochem Pharmacol. 2004;68:971–980
  118. Yeo EJ, Chun YS, Park JW. New anticancer strategies targeting HIF-1. Biochem Pharmacol. 2004;68:1061–1069
  119. Benstead K, Moore JV. Quantitative histological changes in murine tail skin following photodynamic therapy. Br J Cancer. 1989;59:503–509
  120. Deininger MH, Weinschenk T, Morgalla MH, Meyermann R, Schluesener HJ. Release of regulators of angiogenesis following Hypocrellin-A and -B photodynamic therapy of human brain tumor cells. Biochem Biophys Res Commun. 2002;298:520–530
  121. Ferrario A, von Tiehl KF, Rucker N, Schwarz MA, Gill PS, Gomer CJ. Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Res. 2000;60:4066–4069
  122. Ferrario A, Chantrain CF, von Tiehl K, et al. The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model. Cancer Res. 2004;64:2328–2332
  123. Jiang F, Zhang ZG, Katakowski M, et al. Angiogenesis induced by photodynamic therapy in normal rat brains. Photochem Photobiol. 2004;79:494–498
  124. Uehara M, Inokuchi T, Sano K, ZuoLin W. Expression of vascular endothelial growth factor in mouse tumours subjected to photodynamic therapy. Eur J Cancer. 2001;37:2111–2115
  125. Koukourakis MI, Giatromanolaki A, Skarlatos J, et al. Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy. Cancer Res. 2001;61:1830–1832
  126. Henderson BW, Dougherty TJ. How does photodynamic therapy work?. Photochem Photobiol. 1992;55:145–157
  127. Dewhirst MW, Kimura H, Rehmus SW, et al. Microvascular studies on the origins of perfusion-limited hypoxia. Br J Cancer Suppl. 1996;27:S247–S251
  128. Tromberg BJ, Orenstein A, Kimel S, et al. In vivo tumor oxygen tension measurements for the evaluation of the efficiency of photodynamic therapy. Photochem Photobiol. 1990;52:375–385
  129. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–257
  130. Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R, Kroemer G. Cell death by mitotic catastrophe: a molecular definition. Oncogene. 2004;23:2825–2837
  131. Bizik J, Kankuri E, Ristimaki A, Taieb A, Vapaatalo H, Lubitz W, et al. Cell–cell contracts trigger programmed necrosis and induce cyclooxygenase-2 expression. Cell Death Differ. 2004;11:183–195
  132. Leist M, Jaattela M. Triggering of apoptosis by cathepsins. Cell Death Differ. 2001;8:324–326
  133. Yu L, Lenardo MJ, Baehrecke EH. Autophagy and caspases: a new cell death program. Cell Cycle. 2004;3:1124–1126
  134. Leist M, Jaattela M. Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol. 2001;2:589–598
  135. Shi Y. Caspase activation: revisiting the induced proximity model. Cell. 2004;117:855–858
  136. Stroh C, Schulze-Osthoff K. Death by a thousand cuts: an ever increasing list of caspase substrates. Cell Death Differ. 1998;5:997–1000
  137. Martinou JC, Green DR. Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol. 2001;2:63–67
  138. Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309–1312
  139. Chou JJ, Li H, Salvesen GS, Yuan J, Wagner G. Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell. 1999;96:615–624
  140. Bossy-Wetzel E, Green DR. Caspases induce cytochrome c release from mitochondria by activating cytosolic factors. J Biol Chem. 1999;274:17484–17490
  141. Carmody RJ, McGowan AJ, Cotter TG. Reactive oxygen species as mediators of photoreceptor apoptosis in vitro. Exp Cell Res. 1999;248:520–530
  142. Mateo V, Lagneaux L, Bron D, et al. CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia. Nat Med. 1999;5:1277–1284
  143. Fombonne J, Reix S, Rasolonjanahary R, et al. EGF triggers an original, caspase-independent pituitary cell death with heterogeneous phenotype. Mol Biol Cell. 2004;15:4938–4948
  144. Agarwal ML, Clay ME, Harvey EJ, Evans HH, Antunez AR, Oleinick NL. Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells. Cancer Res. 1991;51:5993–5996
  145. Plaetzer K, Kiesslich T, Krammer B, Hammerl P. Characterization of the cell death modes and the associated changes in cellular energy supply in response to AlPcS4-PDT. Photochem Photobiol Sci. 2002;1:172–177
  146. Nagata S, Obana A, Gohto Y, Nakajima S. Necrotic and apoptotic cell death of human malignant melanoma cells following photodynamic therapy using an amphiphilic photosensitizer, ATX-S10(Na). Lasers Surg Med. 2003;33:64–70
  147. Kessel D, Poretz RD. Sites of photodamage induced by photodynamic therapy with a chlorine e6 triacetoxymethyl ester (CAME). Photochem Photobiol. 2000;71:94–96
  148. Lavie G, Kaplinsky C, Toren A, et al. A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy. Br J Cancer. 1999;79:423–432
  149. Xue LY, Chiu SM, Oleinick NL. Photodynamic therapy-induced death of MCF-7 human breast cancer cells: a role for caspase-3 in the late steps of apoptosis but not for the critical lethal event. Exp Cell Res. 2001;263:145–155
  150. Morris RL, Azizuddin K, Lam M, et al. Fluorescence resonance energy transfer reveals a binding site of a photosensitizer for photodynamic therapy. Cancer Res. 2003;63:5194–5197
  151. Kessel D, Luo Y. Photodynamic therapy: a mitochondrial inducer of apoptosis. Cell Death Differ. 1999;6:28–35
  152. Usuda J, Azizuddin K, Chiu SM, Oleinick NL. Association between the photodynamic loss of Bcl-2 and the sensitivity to apoptosis caused by phthalocyanine photodynamic therapy. Photochem Photobiol. 2003;78:1–8
  153. Granville DJ, Levy JG, Hunt DW. Photodynamic treatment with benzoporphyrin derivative monoacid ring A produces protein tyrosine phosphorylation events and DNA fragmentation in murine P815 cells. Photochem Photobiol. 1998;67:358–362
  154. Kessel D, Antolovich M, Smith KM. The role of the peripheral benzodiazepine receptor in the apoptotic response to photodynamic therapy. Photochem Photobiol. 2001;74:346–349
  155. Dougherty TJ, Sumlin AB, Greco WR, Weishaupt KR, Vaughan LA, Pandey RK. The role of the peripheral benzodiazepine receptor in photodynamic activity of certain pyropheophorbide ether photosensitizers: albumin site II as a surrogate marker for activity. Photochem Photobiol. 2002;76:91–97
  156. Morris RL, Varnes ME, Kenney ME, et al. The peripheral benzodiazepine receptor in photodynamic therapy with the phthalocyanine photosensitizer Pc4. Photochem Photobiol. 2002;75:652–661
  157. Belzacq AS, Jacotot E, Vieira HL, et al. Apoptosis induction by the photosensitizer verteporfin: identification of mitochondrial adenine nucleotide translocator as a critical target. Cancer Res. 2001;61:1260–1264
  158. Renno RZ, Delori FC, Holzer RA, Gragoudas ES, Miller JW. Photodynamic therapy using Lu-Tex induces apoptosis in vitro, and its effect is potentiated by angiostatin in retinal capillary endothelial cells. Invest Ophthalmol Vis Sci. 2000;41:3963–3971
  159. Woodburn KW, Fan Q, Miles DR, Kessel D, Luo Y, Young SW. Localization and efficacy analysis of the phototherapeutic lutetium texaphyrin (PCI-0123) in the murine EMT6 sarcoma model. Photochem Photobiol. 1997;65:410–415
  160. Canete M, Ortega C, Gavalda A, et al. Necrotic cell death induced by photodynamic treatment of human lung adenocarcinoma A-549 cells with palladium(II)-tetraphenylporphycene. Int J Oncol. 2004;24:1221–1228
  161. Blank M, Mandel M, Keisari Y, Meruelo D, Lavie G. Enhanced ubiquitinylation of heat shock protein 90 as a potential mechanism for mitotic cell death in cancer cells induced with hypericin. Cancer Res. 2003;63:8241–8247
  162. Thibaut S, Bourre L, Hernot D, Rousset N, Lajat Y, Patrice T. Effects of BAPTA-AM, Forskolin, DSF and Z. VAD fmk on PDT-induced apoptosis and m-THPC phototoxicity on B16 cells. Apoptosis. 2002;7:99–106
  163. Chen JY, Mak NK, Yow CM, et al. The binding characteristics and intracellular localization of temoporfin (mTHPC) in myeloid leukemia cells: phototoxicity and mitochondrial damage. Photochem Photobiol. 2000;72:541–547
  164. He XY, Sikes RA, Thomsen S, Chung LW, Jacques SL. Photodynamic therapy with photofrin II induces programmed cell death in carcinoma cell lines. Photochem Photobiol. 1994;59:468–473
  165. Dellinger M. Apoptosis or necrosis following Photofrin photosensitization: influence of the incubation protocol. Photochem Photobiol. 1996;64:182–187
  166. Bachowski GJ, Pintar TJ, Girotti AW. Photosensitized lipid peroxidation and enzyme inactivation by membrane-bound merocyanine 540: reaction mechanisms in the absence and presence of ascorbate. Photochem Photobiol. 1991;53:481–491
  167. Koukourakis MI, Corti L, Skarlatos J, et al. Clinical and experimental evidence of Bcl-2 involvement in the response to photodynamic therapy. Anticancer Res. 2001;21:663–668
  168. Dahle J, Kaalhus O, Moan J, Steen HB. Cooperative effects of photodynamic treatment of cells in microcolonies. Proc Natl Acad Sci USA. 1997;94:1773–1778
  169. Dahle J, Steen HB, Moan J. The mode of cell death induced by photodynamic treatment depends on cell density. Photochem Photobiol. 1999;70:363–367
  170. Dahle J, Bagdonas S, Kaalhus O, Olsen G, Steen HB, Moan J. The bystander effect in photodynamic inactivation of cells. Biochim Biophys Acta. 2000;1475:273–280
  171. Shao C, Furusawa Y, Kobayashi Y, Funayama T, Wada S. Bystander effect induced by counted high-LET particles in confluent human fibroblasts: a mechanistic study. FASEB J. 2003;17:1422–1427
  172. Oleinick NL, Evans HH. The photobiology of photodynamic therapy: cellular targets and mechanisms. Radiat Res. 1998;150:S146–S156
  173. Fuchs J, Weber S, Kaufmann R. Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy. Free Radic Biol Med. 2000;28:537–548
  174. Di Mascio P, Teixeira PC, Onuki J, et al. DNA damage by 5-aminolevulinic and 4,5-dioxovaleric acids in the presence of ferritin. Arch Biochem Biophys. 2000;373:368–374
  175. Douki T, Onuki J, Medeiros MH, Bechara EJ, Cadet J, Di Mascio P. DNA alkylation by 4,5-dioxovaleric acid, the final oxidation product of 5-aminolevulinic acid. Chem Res Toxicol. 1998;11:150–157
  176. Onuki J, Teixeira PC, Medeiros MH, et al. Is 5-aminolevulinic acid involved in the hepatocellular carcinogenesis of acute intermittent porphyria?. Cell Mol Biol. 2002;48:17–26
  177. Cadet J, Berger M, Decarroz C, et al. Photosensitized reactions of nucleic acids. Biochimie. 1986;68:813–834
  178. Fiel RJ, Datta-Gupta N, Mark EH, Howard JC. Induction of DNA damage by porphyrin photosensitizers. Cancer Res. 1981;41:3543–3545
  179. Woods JA, Traynor NJ, Brancaleon L, Moseley H. The effect of photofrin on DNA strand breaks and base oxidation in HaCaT keratinocytes: a comet assay study. Photochem Photobiol. 2004;79:105–113
  180. Rousset N, Keminon E, Eleouet S, et al. Use of alkaline Comet assay to assess DNA repair after m-THPC-PDT. J Photochem Photobiol B. 2000;56:118–131
  181. Peterson CM, Lu JM, Sun Y, et al. Combination chemotherapy and photodynamic therapy with N-(2-hydroxypropyl) methacrylamide copolymer-bound anticancer drugs inhibit human ovarian carcinoma heterotransplanted in nude mice. Cancer Res. 1996;56:3980–3985
  182. Freitag L, Ernst A, Thomas M, Prenzel R, Wahlers B, Macha HN. Sequential photodynamic therapy (PDT) and high dose brachytherapy for endobronchial tumour control in patients with limited bronchogenic carcinoma. Thorax. 2004;59:790–793
  183. Ross JS, Schenkein DP, Pietrusko R, et al. Targeted therapies for cancer. Am J Clin Pathol. 2004;122:598–609
  184. Finley RS. Overview of targeted therapies for cancer. Am J Health Syst Pharm. 2003;60:S4–S10
  185. Madhusudan S, Ganesan TS. Tyrosine kinase inhibitors in cancer therapy. Clin Biochem. 2004;37:618–635
  186. Park DJ, Lenz HJ. The role of proteosome inhibitors in solid tumors. Ann Med. 2004;36:296–303
  187. La Thangue NB. Histone deacetylase inhibitors and cancer therapy. J Chemother. 2004;16(Suppl. 4):64–67
  188. Rowley PT, Tabler M. Telomerase inhibitors. Anticancer Res. 2000;20:4419–4429

PII: S1572-1000(05)00030-X

doi: 10.1016/S1572-1000(05)00030-X

Photodiagnosis and Photodynamic Therapy
Volume 2, Issue 1 , Pages 1-23 , March 2005

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