Abstract
Photodynamic therapy (PDT) is a promising, minimally invasive cancer therapy. This clinically approved treatment is usually carried out in two stages. In the first step, the photosensitizer (PS) is administered into the body of the patient and allowed to localize at neoplastic regions. Subsequently, in the second step, the neoplastic area is irradiated with specific wavelength of light from a laser source. Upon irradiation the photosensitizer (PS) gets excited and takes part in photochemical reactions by producing free radicals and/or singlet oxygen molecules that induce oxidative stress in cancer cells. These reactive oxygen species (ROS) target many cellular macromolecules like nucleic acids, lipids, proteins, and vitamins. PDT activates many signaling pathways that results in activation of caspases leading to apoptosis. Further, necrosis is the mode of cell death when high doses of PDT were used. PDT generated singlet oxygen molecules activate RIP-mediated necrotic pathway. PDT exerts anticancer activity directly by killing the cancer cells and indirectly by damaging the tumor vasculature and by activating antitumor immunity. In this chapter, the mechanism of PDT-induced oxidative damage of cellular components and cell death through multiple signaling pathways is discussed in detail. Understanding the chemical and biological processes involved in PDT will help in devising ways to increase photodynamic therapeutic efficiency against cancer. The measures to make PDT an efficient cancer therapeutic modality by overcoming cancer cell survival pathways that operate after PDT are also discussed.
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References
Agarwal ML, Larkin HE, Zaidi SIA, Mukhtar H, Oleinick NL (1993) Phospholipid activation triggers apoptosis in photosensitized mouse lymphoma cells. Cancer Res 53:5897–5902
Allison RR, Downie GH, Cuenca R, Hu X, Childs CJH, Sibata CH (2004) Photosensitizers in clinical PDT. Photodiagn Photodyn Ther 1:27–42
Almeida RD, Manadas BJ, Carvalho AP, Duarte CB (2004) Intracellular signaling mechanisms in photodynamic therapy. Biochim Biophys Acta 1704:59–86
Athar M, Mukhtar H, Elmets CA, Zaim MT, Lloyd JR, Bickers DR (1988) In situ evidence for the involvement of superoxide anions in cutaneous porphyrin photosensitization. Biochem Biophys Res Commun 151:1054–1059
Baptista MS, Cadet J, Mascio PD, Ghogare AA, Greer A, Hamblin MR, Lorente C, Nunez SC, Ribeiro MS, Thomas AH, Vignoni M, Yoshimura TM (2017) Type I and type II photosensitized oxidation reactions: guidelines and mechanistic pathways. Photochem Photobiol 93:912–919
Benov L (2015) Photodynamic therapy: current status and future directions. Med Princ Pract 24:14–28
Cadet J, Loft S, Olinski R et al (2012) Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids. Free Radic Res 46:467–481
Caruso JA, Mathieu PA, Joiakim A, Leeson B, Kessel D, Sloane BF, Reiners JJ Jr (2004) Differential susceptibilities of murine hepatoma 1c1c7 and Tao cells to the lysosomal photosensitizer NPe6: Influence of aryl hydrocarbon receptor on lysosomal fragility and protease contents. Mol Pharmacol 65:1016–1028
Castano AP, Demidova TN, Hamblin MR (2004) Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther 1:279–293
Cekaite L, Peng Q, Reiner A, Shahzidi S, Tveito S, Furre IE, Hovig E (2007) Mapping of oxidative stress responses of human tumor cells following photodynamic therapy using hexaminolevulinate. BMC Genomics 8:273–293
Chaloupka R, Obsil T, Plasek J, Sureau F (1999) The effect of hypericin and hypocrellin-A on lipid membranes and membrane potential of 3T3 fibroblasts. Biochim Biophys Acta 1418:39–47
Chilakamarthi U, Giribabu L (2017) Photodynamic therapy: past, present and future. Chem Rec 17:1–29
Chiu SM, Oleinick NL (2001) Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy. Br J Cancer 84:1099–1106
Coupienne I, Fettweis G, Rubio N, Agostinis P, Piette J (2011) 5-ALA-PDT induces RIP3-dependent necrosis in glioblastoma. Photochem Photobiol Sci 10:1868–1878
Dąbrowski JM (2017) Reactive oxygen species in photodynamic therapy: mechanisms of their generation and potentiation. Adv Inorg Chem 70:343–394
Du L, Jiang N, Wang G, Chu Y, Lin W, Qian J, Zhang Y, Zheng J, Chen G (2014) Autophagy inhibition sensitizes bladder cancer cells to the photodynamic effects of the novel photosensitizer chlorophyllin e4. J Photochem Photobiol B Biol 133:1–10
Ferrario A, Rucker N, Wong S, Luna M, Gomer CJ (2007) Survivin, a member of the inhibitor of apoptosis family, is induced by photodynamic therapy and is a target for improving treatment response. Cancer Res 67:4989–4995
Furre IE, Moller MT, Shahzidi S, Nesland JM, Peng Q (2006) Involvement of both caspase dependent and independent pathways in apoptotic induction by hexaminolevulinate mediated photodynamic therapy in human lymphoma cells. Apoptosis 11(11):2031–2042
Girotti AW (2001) Photosensitized oxidation of membrane lipids: reaction pathways, cytotoxic effects, and cytoprotective mechanisms. J Photochem Photobiol B Biol 63:103–113
Girotti AW, Kriska T (2004) Role of lipid hydroperoxides in photo-oxidative stress signaling. Antioxid Redox Signal 6:301–310
Golab J, Nowis D, Skrzycki M, Czeczot H, Baranczyk-Kuzma A, Wilczynski GM, Makowski M, Mroz P, Kozar K, Kaminski R, Jalili A, Kopec M, Grzela T, Jakobisiak M (2003) Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol. A superoxide dismutase inhibitor. J Biol Chem 278:407–414
Grebenova D, Kuzelova K, Smetana K et al (2003) 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 69:71–85
Kessel D, Castelli M (2001) Evidence that bcl-2 is the target of three photosensitizers that induce a rapid apoptotic response. Photochem Photobiol 74:318–322
Korbelik M, Sun J, Cecic I (2005) Photodynamic therapy-induced cell surface expression and release of heat shock proteins: relevance for tumor response. Cancer Res 65:1018–1026
Kralova J, Dvorak M, Koc M, Kral V (2008) p38 MAPK plays an essential role in apoptosis induced by photoactivation of a novel ethylene glycol porphyrin derivative. Oncogene 27:3010–3020
Kroemer G, Jaattela M (2005) Lysosomes and autophagy in cell death control. Nat. Rev Cancer 5:886–897
Maiya BG (2000) Photodynamic therapy (PDT), Basic principles. Resonance 5:6–18
Michaeli A, Feitelson J (1994) Reactivity of singlet oxygen toward amino acids and peptides. Photochem Photobiol 59:284–298
Miller AC, Henderson BW (1986) The influence of cellular glutathione content on cell survival following photodynamic treatment in vitro. Radiat Res 107:83–94
Mohamed Ali S, Chee SK, Yuen GY, Olivo M (2002) Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells, Int. J Mol Med 9:601–616
Mroz P, Bhaumik J, Dogutan DK et al (2009) Imidazole metalloporphyrins as photosensitizers for photodynamic therapy: role of molecular charge, central metal and hydroxyl radical production. Cancer Lett 282:63–76
Mroz P, Yaroslavsky A, Kharkwal GB, Hamblin MR (2011) Cell death pathways in photodynamic therapy of cancer. Cancers (Basel) 3:2516–2539
Noodt BB, Berg K, Stokke T, Peng Q, Nesland JM (1999) Different apoptotic pathways are induced from various intracellular sites by tetraphenylporphyrins and light. Br J Cancer 79:72–81
Oleinick NL, Morris RL, Belichenko I (2002) The role of apoptosis in response to photodynamic therapy: what, where, why, and how. Photochem Photobiol Sci 1:1–21
Reiners JJ, Agostinis P, Berg K, Oleinick NL, Kessel DH (2010) Assessing autophagy in the context of photodynamic therapy. Autophagy 6:7–18
Ruvolo PP, Deng X, Ito T, Carr BK, May WS (1999) Ceramide induces Bcl-2 dephosphorylation via a mechanism involving mitochondrial pp2A. J Biol Chem 274:20296–20300
Sharman WM, Allen CM, Van Lier JE (2000) Role of activated oxygen species in photodynamic therapy. Methods Enzymol 319:376–400
Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics. CA Cancer J Clin 70:7–33
Szokalska A, Makowski M, Nowis D, Wilczynski GM, Kujawa M, Wojcik C, Mlynarczuk-Bialy I, Salwa P, Bil J, Janowska S, Agostinis P, Verfaillie T, Bugajski M, Gietka J, Issat T, Glodkowska E, Mrowka P, Stoklosa T, Hamblin MR, Mroz P, Jakobisiak M, Golab J (2009) Proteasome inhibition potentiates antitumor effects of photodynamic therapy in mice through induction of endoplasmic reticulum stress and unfolded protein response. Cancer Res 69:4235–4243
Takahashi H, Itoh Y, Miyauchi Y, Nakajima S, Sakata I, Yamamoto AI, Iizuka H (2003) Activation of two caspase cascades, caspase 8/3/6 and caspase 9/3/6, during photodynamic therapy using a novel photosensitizer ATX-S10(Na) in normal human keratinocytes. Arch Dermatol Res 295:242–248
Valli F, GarcÃa Vior MC, Roguin LP, Marino J (2020) Crosstalk between oxidative stress-induced apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma. Free Radic Biol Med 152:743–754
Wang HP, Hanlon JG, Rainbow AJ, Espiritu M, Singh G (2002) Up-regulation of Hsp27 plays a role in the resistance of human colon carcinoma HT29 cells to photooxidative stress. Photochem Photobiol 76:98–104
Weyergang A, Berg K, Kaalhus O, Peng Q, Selbo PK (2009) Photodynamic therapy targets the mTOR signaling network in vitro and in vivo. Mol Pharm 6:255–264
Xue LY, Chiu SM, Oleinick NL (2001) Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4. Oncogene 20:3420–3427
Ziółkowska B, Woźniak M, Ziółkowski P (2016) Co-expression of autophagic markers following photodynamic therapy in SW620 human colon adenocarcinoma cells. Mol Med Rep 14:2548–2554
Acknowledgments
The authors sincerely thank DST for the financial support to Ushasri under WOS-A Scheme (SR/WOS-A/LS-1374/2014) (G) and Padma under WOS-A Scheme (SR/WOS-A/CS-1115/2015). We are thankful to DKIM division (IICT Communication No. IICT/Pubs/2021/178) for their support.
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Chilakamarthi, U., Singu, P.S., Giribabu, L. (2022). Photodynamic Therapy-Induced Oxidative Stress for Cancer Treatment. In: Chakraborti, S. (eds) Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-16-5422-0_58
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DOI: https://doi.org/10.1007/978-981-16-5422-0_58
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