Skip to main content

Advertisement

SpringerLink
Log in

Low concentrations of a non-hydrolysable tetra-S-glycosylated porphyrin and low light induces apoptosis in human breast cancer cells via stress of the endoplasmic reticulum

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

Abstract

A water-soluble tetra-S-glycosylated porphyrin (P-Glu4) is absorbed by MDA-MB-231 human breast cancer cells whereupon irradiation with visible light causes necrosis or apoptosis depending on the concentration of the porphyrin and the power of the light. With the same amount of light irradiation power (9.4 W m−2), at 10-20 μM concentrations necrosis is predominantly observed, while at <10 μM concentrations, apoptosis is the principal cause of cell death. Of the various possible pathways for the induction of apoptosis, experiments demonstrate that calcium is released from the endoplasmic reticulum, cytochrome c is liberated from the mitochondria to the cytosol, pro-caspase-3 is activated, poly-(ADP-ribose) polymerase is cleaved, and the chromatin is condensed subsequent to photodynamic treatment of these cells. Confocal microscopy indicates a substantial portion of the P-Glu4 is located in the endoplasmic reticulum at <10 μM. These data indicate that the photodynamic treatment of MDA-MB-231 cells using low concentrations of the P-Glu4 porphyrin and low light induces apoptosis mostly initiated from stress produced to the endoplasmic reticulum.

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. G. Kroemer, B. Dallaporta, M. Resche-Rigon, The mitochondrial death/life regulator in apoptosis and necrosis, Annu. Rev. Physiol., 1998, 60, 619–642.

    Article  CAS  PubMed  Google Scholar 

  2. A. Lawen, Apoptosis-an introduction, BioEssays, 2003, 25, 888–896.

    Article  CAS  PubMed  Google Scholar 

  3. E. D. Sternberg, C. Bruckner and D. Dolphin, Porphyrin-based photosensitizers for use in photodynamic therapy, Tetrahedron, 1998, 54, 4151–4202.

    Article  CAS  Google Scholar 

  4. J. Osterloh and M. G. H. Vicente, Mechanisms of porphyrinoid localization in tumors, J. Porphyrins Phthalocyanines, 2002, 6, 305–324.

    Article  CAS  Google Scholar 

  5. R. Bonnett, Photosensitizers of the porphyrin the phthalocyanine series for photodynamic therapy, Chem. Soc. Rev., 1995, 24, 19–32.

    Article  CAS  Google Scholar 

  6. N. L. Oleinick, R. L. Morris and I. Belichenko, The role of apoptosis in response to photodynamic therapy: what, where, why, and how, Photochem. Photobiol. Sci., 2002, 1, 1–21.

    Article  CAS  PubMed  Google Scholar 

  7. D. Kessel and Y. Luo, Photodynamic therapy: A mitochondrial inducer of apoptosis, Cell Death Differentiation, 1999, 6, 28–35.

    Article  CAS  PubMed  Google Scholar 

  8. X. Chen, L. Hui, D. A. Foster and C. M. Drain, Efficient synthesis and photodynamic activity of porphyrin-saccharide conjugates: targeting and incapacitating cancer cells, Biochemistry, 2004, 43, 10918–10929.

    Article  CAS  PubMed  Google Scholar 

  9. M. E. Varnes, S.-M. Chiu, L.-Y. Xue and N. L. Oleinick, Photodynamic therapy-induced apoptosis in lymphoma cells: Translocation of cytochrome c causes inhibition of respiration as well as caspase activation, Biochem. Biophys. Res. Commun., 1999, 255, 673–679.

    Article  CAS  PubMed  Google Scholar 

  10. D. J. Granville and D. W. C. Hunt, Porphyrin-mediated photosensitization - Taking the apoptosis fast lane, Curr. Opin. Drug Discovery Develop., 2000, 3, 232–243.

    CAS  Google Scholar 

  11. I. Yslas, M. G. Alvarez, C. Marty, G. Mori, E. N. Durantini and V. Rivarola, Expression of Fas antigen and apoptosis caused by 5,10,15,20-tetra(4-methoxyphenyl)porphyrin (TMP) on carcinoma cells: implication for photodynamic therapy, Toxicology, 2000, 149, 69–74.

    Article  CAS  PubMed  Google Scholar 

  12. D. Kessel and Y. Luo, Intracellular sites of photodamage as a factor in apoptotic cell death, J. Porphyrins Phthalocyanines, 2001, 5, 181–184.

    Article  CAS  Google Scholar 

  13. T. J. McGarrity, L. P. Peiffer, D. J. Granville, C. M. Carthy, J. G. Levy, M. Khandelwal and D. W. C. Hunt, Apoptosis associated with esophageal adenocarcinoma: influence of photodynamic therapy, Cancer Lett., 2001, 163, 33–41.

    Article  CAS  PubMed  Google Scholar 

  14. D. Nowis, M. Makowski, T. Stoklosa, M. Legat, T. Issat and J. Golab, Direct tumor damage mechanisms of photodynamic therapy, Acta Biochim. Polonica, 2005, 52, 339–352.

    Article  CAS  Google Scholar 

  15. C. N. Lunardi and A. C. Tedesco, Synergic photosensitizers: A new trend in photodynamic therapy, Curr. Org. Chem., 2005, 9, 813–821.

    Article  CAS  Google Scholar 

  16. K. Plaetzer, T. Kiesslich, C. B. Oberdanner and B. Krammer, Apoptosis following photodynamic tumor therapy: Induction, mechanisms and detection, Curr. Pharm. Design, 2005, 11, 1151–1165.

    Article  CAS  Google Scholar 

  17. R. D. Almeida, B. J. Manadas, A. P. Carvalho and C. B. Duarte, Intracellular signaling mechanisms in photodynamic therapy, Biochim. Biophys. Acta - Rev. Cancer, 2004, 1704, 59–86.

    Article  CAS  Google Scholar 

  18. T.-I. Peng, C.-J. Chang, M.-J. Guo, Y.-H. Wang, J.-S. Yu, H.-Y. Wu and M.-J. Jou, Mitochondria-targeted photosensitizer enhances the photodynamic effect-induced mitochondrial dysfunction and apoptosis, Ann. N. Y. Acad. Sci., 2005, 1042, 419–428.

    Article  CAS  PubMed  Google Scholar 

  19. E. Buytaert, M. Dewaele and P. Agostinis, Molecular effectors of multiple cell death pathways initiated by photodynamic therapy, Biochim. Biophys. Acta - Rev. Cancer, 2007, 1776, 86–107.

    Article  CAS  Google Scholar 

  20. J. C. Reed, Cytochrome c: can’t live with it—can’t live without it, Cell, 1997, 91, 559–562.

    Article  CAS  PubMed  Google Scholar 

  21. A. C. E. Moor, Signaling pathways in cell death and survival after photodynamic therapy, J. Photochem. Photobiol., B, 2000, 57, 1–13.

    Article  CAS  Google Scholar 

  22. P. Pasetto, X. Chen, C. M. Drain and R. W. Franck, Synthesis of hydrolytically stable porphyrin C- and S-glycoconjugates in high yields, Chem. Commun., 2001, 81–82.

    Google Scholar 

  23. X. Chen and C. M. Drain, Photodynamic therapy using carbohydrate conjugated porphyrins, Drug Design Rev. Online, 2004, 1, 215–234.

    Article  CAS  Google Scholar 

  24. C. Xu, B. Bailly-Maitre and J. C. Reed, Endoplasmic reticulum stress: cell life and death decisions, J. Clin. Invest., 2005, 115, 2656–2664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. E. A. Slee, C. Adrain and S. J. Martin, Serial killers: ordering caspase activation events in apoptosis, Cell Death Differentiation, 1999, 6, 1067–1074.

    Article  CAS  PubMed  Google Scholar 

  26. S. Kothakota, T. Azuma, C. Reinhard, A. Klippel, J. Tang, K. Chu, T. J. McGarry, M. W. Kirschner, K. Koths, D. J. Kwiatkowski and L. T. Williams, Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis, Science, 1997, 278, 294–298.

    Article  CAS  PubMed  Google Scholar 

  27. S.-W. Yu, H. Wang, M. F. Poitras, C. Coombs, W. J. Bowers, H. J. Federoff, G. G. Poirier, T. M. Dawson and V. L. Dawson, Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor, Science, 2002, 297, 259–263.

    Article  CAS  PubMed  Google Scholar 

  28. G. de Murcia, J. M. de Murcia, Poly(ADP-ribose) polymerase: a molecular nick-sensor, Trends Biochem. Sci., 1994, 19, 172–176.

    Article  PubMed  Google Scholar 

  29. B. S. P. Reddy, S. M. Sondhi and J. W. Lown, Synthetic DNA minor groove-binding drugs, Pharm. Therap., 1999, 84, 1–111.

    Article  CAS  Google Scholar 

  30. C. M. Drain and X. Gong, Synthesis of meso substituted porphyrins in air without solvents or catalysts, Chem. Commun., 1997, 2117–2118.

    Google Scholar 

  31. J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney and A. M. Marguerettaz, Rothemund and Adler-Longo reactions revisited: Synthesis of tetraphenylporphyrins under equilibrium conditions, J. Org. Chem., 1987, 52, 827–836.

    Article  CAS  Google Scholar 

  32. A. D. Adler, F. R. Longo, J. D. Finarelli, J. Goldmacher, J. Assour and L. Korsakoff, A simplified synthesis for meso-tetraphenylporphine, J. Org. Chem., 1967, 32, 476–476.

    Article  CAS  Google Scholar 

  33. J. Caramelo and A. J. Parodi, How sugars convey information on protein conformation in the endoplasmic reticulum, Seminars Cell Developmental Biol., 2007, 18, 732–742.

    Article  CAS  Google Scholar 

  34. C. M. Drain, X. Gong, V. Ruta, C. E. Soll and P. F. Chicoineau, Combinatorial synthesis and modification of functional porphyrin libraries: identification of new, amphipathic motifs for biomolecule binding, J. Comb. Chem., 1999, 1, 286–290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. M. W. Grinstaff, M. G. Hill, J. A. Labinger and H. B. Gray, Mechanism of catalytic oxygenation of alkanes by halogenated iron porphyrins, Science, 264, 1311–1313.

  36. D. Samaroo, M. Vinodu, X. Chen and C. M. Drain, meso-Tetra(pentafluorophenyl)porphyrin as an efficient platform for combinatorial synthesis and the selection of new photodynamic therapeutics using a cancer cell line, J. Comb. Chem., 2007, 9, 998–1011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. K. Fujimoto, T. Miyata and Y. Aoyama, Saccharide-directed cell recognition and molecular delivery using macrocyclic saccharide clusters: Masking of hydrophobicity to enhance the saccharide specificity, J. Am. Chem. Soc., 2000, 122, 3558–3559.

    Article  CAS  Google Scholar 

  38. M. Lam, N. L. Oleinick, A.-L. Nieminen, Photodynamic therapy-induced apoptosis in epidermoid carcinoma cells. Reactive oxygen species and mitochondrial inner membrane permeabilization, J. Biol. Chem., 2001, 276, 47379–47386.

    Article  CAS  PubMed  Google Scholar 

  39. R. K. Pandey, Recent advances in photodynamic therapy, J. Porphyrins Phthalocyanines, 2000, 4, 368–373.

    Article  CAS  Google Scholar 

  40. M. Srivastava, N. Ahmad, S. Gupta and H. Mukhtar, Involvement of Bcl-2 and Bax in photodynamic therapy-mediated apoptosis. Antisense Bcl-2 oligonucleotide sensitizes RIF 1 cells to photodynamic therapy apoptosis, J. Biol. Chem., 2001, 276, 15481–15488.

    Article  CAS  PubMed  Google Scholar 

  41. Y. Luo and D. Kessel, Initiation of apoptosis versus necrosis by photodynamic therapy with chloroaluminum phthalocyanine, Photochem. Photobiol., 1997, 66, 479–483.

    Article  CAS  PubMed  Google Scholar 

  42. A. C. E. Moor, Signaling pathways in cell death and survival after photodynamic therapy, J. Photochem. Photobiol., B, 2000, 57, 1–13.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Hunter College and Graduate Center of the City University of New York, 695 Park Avenue, New York, NY, 10065, USA

    Sebastian Thompson, Xin Chen & Charles Michael Drain

  2. Department of Biological Sciences, Hunter College and Graduate Center of the City University of New York, 695 Park Avenue, New York, NY, 10065, USA

    Li Hui, Alfredo Toschi & David A. Foster

  3. The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

    Charles Michael Drain

Authors
  1. Sebastian Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alfredo Toschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David A. Foster
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Charles Michael Drain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles Michael Drain.

Additional information

Electronic supplementary information (ESI) available: Fluorescence images of P-Glu4 in MDA-MB-231 cells, detection of pro-caspase-3 cleavage and calcium released from ER. See DOI: 10.1039/b806536e

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thompson, S., Chen, X., Hui, L. et al. Low concentrations of a non-hydrolysable tetra-S-glycosylated porphyrin and low light induces apoptosis in human breast cancer cells via stress of the endoplasmic reticulum. Photochem Photobiol Sci 7, 1415–1421 (2008). https://doi.org/10.1039/b806536e

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/b806536e

Search

Navigation