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Effect of DTPP-mediated photodynamic therapy on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line

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Abstract

Photodynamic therapy (PDT) involves the administration and activation of photosensitizing reagents in cancer tissues to induce cytotoxicity. Here we examined the effects of 5-5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP) -mediated PDT on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line. LA795 murine lung adenocarcinoma cell line was used in the study, with cellular uptake of DTPP being quantified by a UV-visible spectrophotometer. The subcellular localization of DTPP was detected by confocal laser scanning microscopy, alteration of cell morphology after PDT was observed by an inverted light microscope, and late-stage apoptosis was examined by terminal dUTP nick end labeling (TUNEL) . The effects of influencing factors on cytotoxicity of PDT in LA795 cells was investigated with varying concentrations of DTPP, energy densities, power densities, and antioxidants by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Effects of PDT on cell cycle and plasma membrane integrity were studied by flow cytometry analysis. The uptake of DTPP by LA795 cells reached maximum after incubation for 24 h. Confocal laser scanning microscopy showed that DTPP was mainly in the mitochondrion, and slight localization was detected in the lysosomes. Cellular inhibitory effects increased with increased irradiation dose and DTPP concentration, while unactivated DTPP had low toxicity. Flow cytometry analysis revealed that DTPP-PDT-treated cells showed S phase arrest. Cell membrane damage initiation, repair, and irreversible damage were observed at 2, 4, and 5 h after DTPP-PDT , respectively. Together, our results demonstrated cell apoptosis, compromised viability, and cell cycle S phase arrest of LA795 in response to DTPP-PDT , while no effect on the lung cancer cells was observed with irradiation or photosensitizer treatment alone.

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References

  1. Marks P (1999) Photodynamic therapy for central nervous system tumors: achievements and prospects. Br J Neurosurg 13(4):349–351

    Article  CAS  PubMed  Google Scholar 

  2. Marks PV, Belchetz PE, Saxena A et al (2000) Effect of photo-dynamic therapy on recurrent pituitary adenomas: clinical phase I/ II trial—an early report. Br J Neurosurg 14:317–325

  3. Allison RR, Sibata CH (2010) Oncological photodynamic therapy photosensitizers: a clinical review. Photodiagn Photodyn Ther 7:61–75

    Article  CAS  Google Scholar 

  4. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  5. Kessel D, Luo Y, Mathieu P, Reiners JJ Jr (2000) Determinants of apoptotic response to lysosomal photodamage. Photochem Photobiol 71:196–200

    Article  CAS  PubMed  Google Scholar 

  6. Kessel D, Vicente MG, Reiners JJ (2006) Initiation of apoptosis and autophagy by photodynamic therapy. Lasers Surg Med 38:482–488

    Article  PubMed Central  PubMed  Google Scholar 

  7. Chi L (2005) Technological developments in laser-guided cancer screening and therapy. Univ Toronto Med J 83:119–120

    Google Scholar 

  8. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q (1998) Photodynamic therapy. J Natl Cancer Inst 90:889–905

    Article  CAS  PubMed  Google Scholar 

  9. Yang VXD, Muller PJ, Herman P, Wilson BC (2003) A multispectral fluorescence imaging system: design and initial clinic tests in intra-operative Photofrin-photodynamic therapy of brain tumors. Lasers Surg Med 32(3):224–232

    Article  PubMed  Google Scholar 

  10. Chen J, Wang Y, Liu T (2011) Photodynamic efficiency of new porphyrin-typed drug on HGC27 and MGC803 cells. Int J Biomed Eng 34(3):154–157

    CAS  Google Scholar 

  11. Yslas E, Rivarola V, Durantini EN (2005) Synthesis and photodynamic activity of zinc(II) phthalocyanine derivatives bearing methoxy and trifluoromethylbenzyloxy substituents in homogeneous and biological media. Bioorg Med Chem 13:39–46

    Article  CAS  PubMed  Google Scholar 

  12. Macdonald IJ, Dougherty TJ (2001) Basic principles of photodynamic therapy. J Porphyr Phthalocyan 5:105–129

    Article  CAS  Google Scholar 

  13. Krishnamurthy S, Powers SK, Witmer P, Brown T (2000) Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors. Lasers Surg Med 27:224–234

    Article  CAS  PubMed  Google Scholar 

  14. Tomioka Y, Kushibiki T, Awazu K (2010) Evaluation of oxygen consumption of culture medium and in vitro photodynamic effect of talaporfin sodium in lung tumor cells. Photomed Laser Surg 28:385–390

  15. Buytaert E, Dewaele M, Agostinis P (2007) Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochim Biophy Acta 1776:86–107

    CAS  Google Scholar 

  16. Henderson BW, Busch TM, Snyder JW (2006) Fluence rate as a modulator of PDT mechanisms. Lasers Surg Med 38:489–493

    Article  PubMed  Google Scholar 

  17. Harrod-Kim P (2006) Tumor ablation with photodynamic therapy: introduction to mechanism and clinical applications. J Vasc Interv Radiol 17:1441–1448

    Article  PubMed  Google Scholar 

  18. Zhu TC, Finlay JC (2008) The role of photodynamic therapy (PDT) physics. Med Phys 35:3127–3136

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Yin H, Li Y, Zheng Y, Ye X, Zheng L, Li C, Xue Z (2012) Photoinactivation of cell-free human immuno deficiency virus by hematoporphyrin monomethyl ether. Lasers Med Sci 27:943–950

    Article  PubMed Central  PubMed  Google Scholar 

  20. Gruber J, Fong S, Chen C-B , Yoong S, Pastorin G, Schaffer S, Cheah I, Halliwell B (2013) Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing. Biotechnol Adv 31:563–592

    Article  CAS  PubMed  Google Scholar 

  21. Pazos MC, Nader HB (2007) Effect of photodynamic therapy on the extracellular matrix and associated components. Braz J Med Biol Res 40:1025–1035

    Article  CAS  PubMed  Google Scholar 

  22. Ratcliffe SL, Matthews EK (1995) Modification of the photodynamic action of delta-aminolaevulinic acid (ALA) on rat pancreatoma cells by mitochondrial benzodiazepine receptor ligands. Br J Cancer 71:300–305

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Verma A, Facchina SL, Hirsch DJ, Song SY, Dillahey LF, Williams JR, Snyder SH (1998) Photodynamic tumor therapy: mitochondrial benzodiazepine receptors as a therapeutic target. Mol Med 4:40–45

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Kessel D, Luo Y (1998) Mitochondrial photodamage and PDT-induced apoptosis. J Photochem Photobiol B 42:89–95

    Article  CAS  PubMed  Google Scholar 

  25. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Kessel D, Luo Y, Deng Y, Chang CK (1997) The role of subcellular localization in initiation of apoptosis by photodynamic therapy. Photochem Photobiol 65:422–426

    Article  CAS  PubMed  Google Scholar 

  27. Haywood-Smalla SL, Vernona DI, Griffithsb J, Schofieldb J, Brown SB (2006) Phthalocyanine-mediated photodynamic therapy induces cell death and a G0/G1 cell cycle arrest in cervical cancer cells. Biochem Biophys Res Commun 339:569–576

    Article  Google Scholar 

  28. Meikrantz W, Gisselbrecht S, Tam SW, Schlegel R (1994) Activation of cyclin A-dependent protein kinases during apoptosis. Natl Acad Sci 91(9):3754–3758

    Article  CAS  Google Scholar 

  29. Lukšienė Z (2003) Photodynamic therapy: mechanism of action and ways to improve the efficiency of treatment. Medicina 39:1137–1150

    PubMed  Google Scholar 

  30. Van Hillegers R, Kort WJ, Wilson JHP (1994) Current status of photodynamic therapy in oncology. Drugs 48:510–527

    Article  Google Scholar 

  31. Yao JA, Jiang M, Tseng GN (1997) Mechanism of enhancement of slow delayed rectifier current by extracellular sulfhydryl modification [J]. Am J Physiol 273:208–219

    Google Scholar 

  32. Chiamvimonvat N, O’Rourke B, Kamp TJ et al (1995) Functional consequences of sulfhydryl modification in the pore-forming subunits of cardiovascular Ca2+ and Na+ channels [J]. Circ Res 76:325–334

  33. Xianting L, Cheng Y (2013) Enantiomer-specific profenofos-induced cytotoxicity and DNA damage mediated by oxidative stress in rat adrenal pheochromocytoma (PC12) cells. J Appl Toxicol 34(2):166–175

    Google Scholar 

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Acknowledgments

This work was supported by the Excellent Youth Foundation of Hebei Educational Committee (YQ2014008) of Hebei Province of China, grants from the Natural Science Foundation of Hebei North University (ZD201310, CXRC1325), and the Natural Science Foundation of Hebei Province of China (No. H2012405016).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Respiratory Medicine, The First Affiliated Hospital of Hebei North University, 075000, Zhangjiakou, China

    Jianhua Liu, Zhihua Zhang & Xiulong Zhang

  2. Department of Pharmacology, Hebei North University, 075000, Zhangjiakou, China

    Liqing Zheng, Li Zhang, Lixia Shen & Haixia Qiao

  3. Laboratory of Laser Medicine, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, 300192, Tianjin, China

    Yingxin Li

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  1. Jianhua Liu
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  4. Zhihua Zhang
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  5. Li Zhang
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Correspondence to Liqing Zheng or Yingxin Li.

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Liu, J., Zheng, L., Li, Y. et al. Effect of DTPP-mediated photodynamic therapy on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line. Lasers Med Sci 30, 181–191 (2015). https://doi.org/10.1007/s10103-014-1637-x

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  • DOI: https://doi.org/10.1007/s10103-014-1637-x

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