Skip to main content
SpringerLink
Log in

Apoptosis and associated phenomena as a determinants of the efficacy of photodynamic therapy

  • Perspective
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Failure of neoplastic cells to respond to conventional chemotherapy is usually associated with factors that limit access of drugs to subcellular sites, differences in cell-cycle kinetics or mutations leading to loss of drug-activation pathways or other processes that govern response factors. For PDT, efficacy depends mainly on selective uptake of photosensitizers by neoplastic cells, oxygenation levels, the suitable direction of irradiation and the availability of pathways to cell death that are highly conserved among mammalian cell types. While it is possible to engineer PDT-resistant cell types, current evidence suggests that the major obstacles to cancer control relate to drug, light and oxygen distribution. This review discusses some of the factors that can govern PDT-induced cell death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Notes and references

  1. M. Visentin, R. Zhao, I. D. Goldman, The antifolates, Hematol. Oncol. Clin. North Am., 2012, 26, 629–648.

    Article  PubMed  PubMed Central  Google Scholar 

  2. J. M. Drake, J. K. Lee, O. N. Witte, Clinical targeting of mutated and wild-type protein tyrosine kinases in cancer, Mol. Cell. Biol., 2014, 34, 1722–1732.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. A. Casas, G. Di Venosa, T. Hasan, A. Batlle, Mechanisms of resistance to photodynamic therapy, Curr. Med. Chem., 2011, 18, 2486–2515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. G. Singh, B. Wilson, S. Sharkey, G. Browman, P. Deschamps, Resistance to photodynamic therapy in radiation induced fibrosarcoma-1 and chinese hamster ovary-multi-drug resistant cells in vitro, Photochem. Photobiol., 1991, 54, 307–312.

    Article  CAS  PubMed  Google Scholar 

  5. M. Luna, C. Gomer, Isolation and initial characterization of mouse tumor cells resistant to porphyrin mediated photodynamic therapy, Cancer Res., 1991, 51, 4243–4249.

    CAS  PubMed  Google Scholar 

  6. T. J. Dougherty, Photodynamic Therapy-new approaches, Semin. Surg. Oncol., 1989, 5, 6–16.

    Article  CAS  PubMed  Google Scholar 

  7. P. Agostinis, K. Berg, K. Cengel, T. Foster, A. Girotti, S. Gollnick, S. Hahn, M. Hamblin, A. Juzeniene, D. Kessel, M. Korbelik, J. Moan, P. Mroz, D. Nowis, J. Piette, B. Wilson, J. Golab, Photodynamic therapy of cancer: an update, CA-Cancer J. Clin., 2011, 61, 250–281.

    Article  PubMed  PubMed Central  Google Scholar 

  8. G. T. WIlliams, Programmed cell death: apoptosis and oncogenesis, Cell, 1991, 65, 1097–1098.

    Article  CAS  PubMed  Google Scholar 

  9. X. Liu, C. N. Kim, J. Yang, R. Jemmerson, X. Wang, Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c, Cell, 1996, 86, 147–157.

    Article  CAS  PubMed  Google Scholar 

  10. S. Sharkey, B. Wilson, R. Moorehead, G. Singh, Mitochondrial alterations in Photodynamic Therapy resistant cells, Cancer Res., 1993, 53, 4994–4999.

    CAS  PubMed  Google Scholar 

  11. M. M. Dix, G. M. Simon, B. F. Cravatt, Global identification of caspase substrates using PROTOMAP (protein topography and migration analysis platform), Methods. Mol. Biol., 2014, 1133, 61–70.

    Article  CAS  PubMed  Google Scholar 

  12. T. Verfaillie, P. A. de Witte, J. Piette, P. Agostinis, Autophagy pathways activated in response to PDT contribute to cell resistance against ROS damage, J. Cell Mol. Med., 2011, 15, 1402–1414.

    Article  PubMed  CAS  Google Scholar 

  13. V. Inguscio, E. Panzarini, L. Dini, Autophagy Contributes to the Death/Survival Balance in Cancer Photo Dynamic Therapy, Cells, 2012, 1, 464–491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. M. Andrzejak, M. Price, D. H. Kessel, Apoptotic and autophagic responses to photodynamic therapy in 1c1c7 murine hepatoma cells, Autophagy, 2011, 7, 979–984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. M. L. Agarwal, M. E. Clay, E. J. Harvey, N. L. Oleinick, Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells, Cancer Res., 1991, 51, 5993–5936.

    CAS  PubMed  Google Scholar 

  16. H.-R. C. Kim, Y. Luo, G. Li, D. Kessel, Enhanced apoptotic response to photodynamic therapy after bcl-2 transfection, Cancer Res., 1999, 59, 3429–3432.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. L.-Y. Xue, S.-M. Chiu, N. L. Oleinick, Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4, Oncogene, 2001, 20, 3420–3427.

    Article  CAS  PubMed  Google Scholar 

  18. S. Sinha, B. Levine, The autophagy effector Beclin 1: a novel BH3-only protein, Oncogene, 2008, 27Suppl 1, S137–S148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. J. He, M. Agarwal, H. Larkin, L. Friedman, L. Xue, N. L. Oleinick, The induction of partial resistance to photodynamic therapy by the protooncogene Bcl-2, Photochem. Photobiol., 1996, 64, 845–852.

    Article  CAS  PubMed  Google Scholar 

  20. T. Kawaguchi, S. Yamamoto, N. Naka, K. Okishio, S. Atagi, M. Ogawara, S. Hosoe, M. Kawahara, K. Furuse, Immunohistochemical analysis of Bcl-2 protein in early squamous cell carcinoma of the bronchus treated with photodynamic therapy, Br. J. Cancer, 2000, 82, 418–423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. J. Reiners, J. Caruso, P. Mathieu, B. Chelladurai, X. Yin, D. Kessel, Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves Bid cleavage, Cell Death Differ., 2002, 9, 934–944.

    Article  CAS  PubMed  Google Scholar 

  22. S. M. Chiu, L. Y. Xue, M. Lam, M. E. Rodriguez, P. Zhang, M. E. Kenney, A. L. Nieminen, N. L. Oleinick, A requirement for bid for induction of apoptosis by photodynamic therapy with a lysosome- but not a mitochondrion-targeted photosensitizer, Photochem. Photobiol., 2010, 86, 1161–1173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. D. Kessel, M. Price, J. Reiners, ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage, Autophagy, 2012, 8, 1333–1341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. D. Kessel, Y. Luo, Y. Deng, C. K. Chang, The role of subcellular localization in initiation of apoptosis by photodynamic therapy, Photochem. Photobiol., 1997, 65, 422–426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. H. Nakamura, Y. Suzuki, M. Takeichi, T. Saito, M. Takayama, K. Aizawa, Morphologic evaluation of the antitumor activity of photodynamic therapy (PDT) using mono-L-aspartyl chlorin e6 (NPe6) against uterine cervical carcinoma cell lines, Int. J. Gynecol. Cancer, 2002, 12, 177–186.

    Article  PubMed  Google Scholar 

  26. N. Madar-Balakirski, C. Tempel-Brami, V. Kalchenko, O. Brenner, D. Varon, A. Scherz, Y. Salomon, Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP) with Tookad, PLoS One, 2010, 5, e10282.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. D. Ackerman, M. C. Simon, Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment, Trends Cell. Biol., 2014, 24, 472–478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. M. Price, L. Heilbrun, D. Kessel, Effects of the oxygenation level on formation of different reactive oxygen species during photodynamic therapy, Photochem. Photobiol., 2013, 89, 683–686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. D. Kessel, J. Reiners, Enhanced Efficacy of Photodynamic Therapy via a Sequential Targeting Protocol, Photochem. Photobiol., 2014, 90, 889–895.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. S. Saggu, H. Hung, G. Quiogue, J. Lemasters, A. Nieminen, Lysosomal signaling enhances mitochondria-mediated photodynamic therapy in A431 cancer cells: role of iron, Photochem. Photobiol., 2012, 88, 461–468.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. X. Zheng, J. Morgan, S. K. Pandey, Y. Chen, E. Tracy, H. Baumann, J. R. Missert, C. Batt, J. Jackson, D. A. Bellnier, B. W. Henderson, R. K. Pandey, Conjugation of 2-(1′-hexyloxyethyl)- 2-devinylpyropheophorbide-a (HPPH) to carbohydrates changes its subcellular distribution and enhances photodynamic activity in vivo, J. Med. Chem., 2009, 52, 4306–4318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. I. Georgakoudi, T. H. Foster, Effects of the subcellular redistribution of two nile blue derivatives on photodynamic oxygen consumption, Photochem. Photobiol., 1998, 68, 115–122.

    Article  CAS  PubMed  Google Scholar 

  33. L. Cincotta, D. Szeto, E. Lampros, T. Hasan, A. H. Cincotta, Benzophenothiazine and benzoporphyrin derivative combination phototherapy effectively eradicates large murine sarcomas, Photochem. Photobiol., 1996, 63, 229–237.

    Article  CAS  PubMed  Google Scholar 

  34. M. F. Wei, M. W. Chen, K. C. Chen, P. J. Lou, S. Y. Lin, S. C. Hung, M. Hsiao, C. J. Yao, M. J. Shieh, Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells, Autophagy, 2014, 10, 1179–1192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. M. Dewaele, W. Martinet, N. Rubio, T. Verfaillie, P. A. de Witte, J. Piette, P. Agostinis, Autophagy pathways activated in response to PDT contribute to cell resistance against ROS damage, J. Cell Mol. Med., 2011, 15, 1402–1414.

    Article  CAS  PubMed  Google Scholar 

  36. A. D. Garg, P. Agostinis, ER stress, autophagy and immunogenic cell death in photodynamic therapy-induced anti-cancer immune responses, Photochem. Photobiol. Sci., 2014, 13, 474–487.

    Article  CAS  PubMed  Google Scholar 

  37. N. Rubio, J. Verrax, M. Dewaele, T. Verfaillie, T. Johansen, J. Piette, P. Agostinis, p38(MAPK)-regulated induction of p62 and NBR1 after photodynamic therapy promotes autophagic clearance of ubiquitin aggregates and reduces reactive oxygen species levels by supporting Nrf2-antioxidant signaling, Free Radicals Biol. Med., 2014, 67, 292–303.

    Article  CAS  Google Scholar 

  38. L. Xue, J. He, N. L. Oleinick, Promotion of photodynamic therapy-induced apoptosis by stress kinases, Cell Death Differ., 1999, 6, 855–864.

    Article  CAS  PubMed  Google Scholar 

  39. R. Bhowmick, A. W. Girotti, Cytoprotective signaling associated with nitric oxide upregulation in tumor cells subjected to photodynamic therapy-like oxidative stress, Free Radicals Biol. Med., 2013, 57, 39–48.

    Article  CAS  Google Scholar 

  40. M. Inaba, R. K. Johnson, Decreased retention of actinomycin D as the basis for cross-resistance in anthracycline- resistant sublines of P388 leukemia, Cancer Res., 1977, 37, 4629–4634.

    CAS  PubMed  Google Scholar 

  41. I. Rizvi, S. Anbil, N. Alagic, J. Celli, L. Z. Zheng, A. Palanisami, M. D. Glidden, B. W. Pogue, T. Hasan, PDT dose parameters impact tumoricidal durability and cell death pathways in a 3D ovarian cancer model, Photochem. Photobiol., 2013, 89, 942–952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. X. Lou, G. Kim, H. Yoon, Y. Koo, E. K. Lee, R. Kopelmanb, E. Yoon, A high-throughput photodynamic therapy screening platform with on-chip control of multiple microenvironmental factors, Lap Chip, 2014, 14, 892–901.

    Article  CAS  Google Scholar 

  43. Y. Yang, X. Yang, J. Zou, C. Jia, Y. Hu, H. Du, H. Wang, Evaluation of photodynamic therapy efficiency using an in vitro three-dimensional microfluidic breast cancer tissue model, Lab Chip, 2014 10.1039/c4lc01065e

    Google Scholar 

  44. S. Anbil, I. Rizvi, J. P. Celli, N. Alagic, B. W. Pogue, T. Hasan, Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer, J. Biomed. Opt., 2013, 18, 098004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    David Kessel

Authors
  1. David Kessel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kessel, D. Apoptosis and associated phenomena as a determinants of the efficacy of photodynamic therapy. Photochem Photobiol Sci 14, 1397–1402 (2015). https://doi.org/10.1039/c4pp00413b

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c4pp00413b

Search

Navigation