Skip to main content
SpringerLink
Log in

Necrosis predominates in the cell death of human colon adenocarcinoma HT-29 cells treated under variable conditions of photodynamic therapy with hypericin

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

Abstract

Photodynamic therapy (PDT) represents a new rapidly-developing anticancer approach based on administration of a non- or weakly-toxic photosensitizer and its activation with light of appropriate wavelength. Hypericin, one of the promising photosensitizers, is known to induce apoptosis with high efficiency in various cell line models. However, here we report the prevalence of necrosis accompanied by suppression of caspase-3 activation in colon adenocarcinoma HT-29 cells exposed to an extensive range of PDT doses evoked by variations in two variables—hypericin concentration and light dose. Necrosis was the principal mode of cell death despite different PDT doses and the absence of anti-apoptotic Bcl-2 expression, even if the same condition induced caspase-3 activity at similar toxicity in HeLa cells. Introduction of Bcl-2 into HT-29 cells invoked caspase-3 activation, changed the Bcl-XL expression pattern, increased the apoptosis ratio with no effect on overall toxicity, and supported arrest in the G2/M-phase of cell cycle. Since it is known that Bcl-2 suppression in HT-29 is reversible and linked to the over-expression of mutated p53 and also considering our data, we suggest that the mutation in p53 and events linked to this feature may play a role in cell death signalling in HT-29 colon cancer cells.

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

References

  1. T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, Q. Peng, J. Natl. Cancer Inst., 1998, 90, 889–905.

    Article  CAS  PubMed  Google Scholar 

  2. P. Agostinis, A. Vantieghem, W. Merlevede, P. A. de Witte, Int. J. Biochem. Cell Biol., 2002, 34, 221–241.

    Article  CAS  PubMed  Google Scholar 

  3. R. W. Redmond, J. N. Gamlin, Photochem. Photobiol., 1999, 70, 391–475.

    Article  CAS  PubMed  Google Scholar 

  4. E. Fox, R. F. Murphy, C. L. McCully, P. C. Adamson, Cancer Chemother. Pharmacol., 2001, 47, 41–44.

    Article  CAS  PubMed  Google Scholar 

  5. J. M. Jacobson, L. Feinman, L. Liebes, N. Ostrow, V. Koslowski, A. Tobia, B. E. Cabana, D. Lee, J. Spritzler, A. M. Prince, Antimicrob. Agents Chemother., 2001, 45, 517–524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. P. Agostinis, A. Vandenbogaerde, A. Donella-Deana, L. A. Pinna, K. T. Lee, J. Goris, W. Merlevede, J. R. Vandenheede, P. De Witte, Biochem. Pharmacol., 1995, 49, 1615–1622.

    Article  CAS  PubMed  Google Scholar 

  7. R. Chaloupka, T. Obsil, J. Plasek, F. Sureau, Biochim. Biophys. Acta, 1999, 1418, 39–47.

    Article  CAS  PubMed  Google Scholar 

  8. C. Hadjur, M. J. Richard, M. O. Parat, P. Jardon, A. Favier, Photochem. Photobiol., 1996, 64, 375–381.

    Article  CAS  PubMed  Google Scholar 

  9. A. Vantieghem, Y. Xu, W. Declercq, P. Vandenabeele, G. Denecker, J. R. Vandenheede, W. Merlevede, P. A. de Witte, P. Agostinis, Photochem. Photobiol., 2001, 74, 133–142.

    Article  CAS  PubMed  Google Scholar 

  10. E. Delaey, A. Vandenbogaerde, W. Merlevede, P. de Witte, J. Photochem. Photobiol., B, 2000, 56, 19–24.

    Article  CAS  Google Scholar 

  11. T. Utsumi, M. Okuma, T. Kanno, Y. Takehara, T. Yoshioka, Y. Fujita, A. A. Horton, K. Utsumi, Biochem. Pharmacol., 1995, 50, 655–662.

    Article  CAS  PubMed  Google Scholar 

  12. R. Chaloupka, P. X. Petit, N. Israel, F. Sureau, FEBS Lett., 1999, 462, 295–301.

    Article  CAS  PubMed  Google Scholar 

  13. P. Solar, I. Cavarga, J. Hofmanova, M. Cekanova-Figurova, P. Miskovsky, P. Brezani, G. Hrckova, A. Kozubik, P. Fedorocko, Planta Med., 2002, 68, 658–660.

    Article  CAS  PubMed  Google Scholar 

  14. S. Marchal, A. Fadloun, E. Maugain, M. A. D’Hallewin, F. Guillemin, L. Bezdetnaya, Biochem. Pharmacol., 2005, 69, 1167–1176.

    Article  CAS  PubMed  Google Scholar 

  15. M. Barberi-Heyob, P. O. Vedrine, J. L. Merlin, R. Millon, J. Abecassis, M. F. Poupon, F. Guillemin, Int. J. Oncol., 2004, 24, 951–958.

    CAS  PubMed  Google Scholar 

  16. N. Zacal, M. Espiritu, G. Singh, A. J. Rainbow, Biochem. Biophys. Res. Commun., 2005, 331, 648–657.

    Article  CAS  PubMed  Google Scholar 

  17. G. J. Peters, B. van Triest, H. H. Backus, C. M. Kuiper, C. L. van der Wilt, H. M. Pinedo, Eur. J. Cancer, 2000, 36, 916–924.

    Article  CAS  PubMed  Google Scholar 

  18. A. Vaculova, J. Hofmanova, K. Soucek, L. Andera, A. Kozubik, FEBS Lett., 2004, 577, 309–313.

    Article  CAS  PubMed  Google Scholar 

  19. U. K. Laemmli, Nature, 1970, 227, 680–685.

    Article  CAS  PubMed  Google Scholar 

  20. B. Vojtesek, J. Bartek, C. A. Midgley, D. P. Lane, J. Immunol. Methods, 1992, 151, 237–244.

    Article  CAS  PubMed  Google Scholar 

  21. A. R. Kamuhabwa, P. M. Agostinis, M. A. D’Hallewin, L. Baert, P. A. de Witte, Photochem. Photobiol., 2001, 74, 126–132.

    Article  CAS  PubMed  Google Scholar 

  22. J. Piette, C. Volanti, A. Vantieghem, J. Y. Matroule, Y. Habraken, P. Agostinis, Biochem. Pharmacol., 2003, 66, 1651–1659.

    Article  CAS  PubMed  Google Scholar 

  23. A. Vantieghem, Y. Xu, Z. Assefa, J. Piette, J. R. Vandenheede, W. Merlevede, P. A. De Witte, P. Agostinis, J. Biol. Chem., 2002, 277, 37718–37731.

    Article  CAS  PubMed  Google Scholar 

  24. P. Agostinis, Z. Assefa, A. Vantieghem, J. R. Vandenheede, W. Merlevede, P. De Witte, Adv. Enzyme Regul., 2000, 40, 157–182.

    Article  CAS  PubMed  Google Scholar 

  25. S. M. Ali, M. Olivo, Int. J. Oncol., 2003, 22, 1181–1191.

    CAS  PubMed  Google Scholar 

  26. A. Vantieghem, Z. Assefa, P. Vandenabeele, W. Declercq, S. Courtois, J. R. Vandenheede, W. Merlevede, P. de Witte, P. Agostinis, FEBS Lett., 1998, 440, 19–24.

    Article  CAS  PubMed  Google Scholar 

  27. X. Y. Shen, N. Zacal, G. Singh, A. J. Rainbow, Photochem. Photobiol., 2005, 81, 306–313.

    Article  CAS  PubMed  Google Scholar 

  28. M. Weller, Cell Tissue Res., 1998, 292, 435–445.

    Article  CAS  PubMed  Google Scholar 

  29. N. R. Rodrigues, A. Rowan, M. E. Smith, I. B. Kerr, W. F. Bodmer, J. V. Gannon, D. P. Lane, Proc. Natl. Acad. Sci. USA, 1990, 87, 7555–7559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D. J. Park, H. Nakamura, A. M. Chumakov, J. W. Said, C. W. Miller, D. L. Chen, H. P. Koeffler, Oncogene, 1994, 9, 1899–1906.

    CAS  PubMed  Google Scholar 

  31. G. Singh, M. Espiritu, X. Y. Shen, J. G. Hanlon, A. J. Rainbow, Photochem. Photobiol., 2001, 73, 651–656.

    Article  CAS  PubMed  Google Scholar 

  32. G. Kroemer, Nat. Med., 1997, 3, 614–620.

    Article  CAS  PubMed  Google Scholar 

  33. G. Lavie, C. Kaplinsky, A. Toren, I. Aizman, D. Meruelo, Y. Mazur, M. Mandel, Br. J. Cancer, 1999, 79, 423–432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. S. Shimizu, Y. Eguchi, W. Kamiike, S. Waguri, Y. Uchiyama, H. Matsuda, Y. Tsujimoto, Oncogene, 1996, 13, 21–29.

    CAS  PubMed  Google Scholar 

  35. E. H. Cheng, D. G. Kirsch, R. J. Clem, R. Ravi, M. B. Kastan, A. Bedi, K. Ueno, J. M. Hardwick, Science, 1997, 278, 1966–1968.

    Article  CAS  PubMed  Google Scholar 

  36. R. U. Janicke, P. Ng, M. L. Sprengart, A. G. Porter, J. Biol. Chem., 1998, 273, 15540–15545.

    Article  CAS  PubMed  Google Scholar 

  37. M. Woo, R. Hakem, M. S. Soengas, G. S. Duncan, A. Shahinian, D. Kagi, A. Hakem, M. McCurrach, W. Khoo, S. A. Kaufman, G. Senaldi, T. Howard, S. W. Lowe, T. W. Mak, Genes Dev., 1998, 12, 806–819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. E. A. Slee, C. Adrain, S. J. Martin, J. Biol. Chem., 2001, 276, 7320–7326.

    Article  CAS  PubMed  Google Scholar 

  39. G. M. Shah, R. G. Shah, G. G. Poirier, Biochem. Biophys. Res. Commun., 1996, 229, 838–844.

    Article  CAS  PubMed  Google Scholar 

  40. C. A. Casiano, R. L. Ochs, E. M. Tan, Cell Death Differ., 1998, 5, 183–190.

    Article  CAS  PubMed  Google Scholar 

  41. C. Soldani, A. I. Scovassi, Apoptosis, 2002, 7, 321–328.

    Article  CAS  PubMed  Google Scholar 

  42. C. D. Scatena, Z. A. Stewart, D. Mays, L. J. Tang, C. J. Keefer, S. D. Leach, J. A. Pietenpol, J. Biol. Chem., 1998, 273, 30777–30784.

    Article  CAS  PubMed  Google Scholar 

  43. H. Y. Du, M. Olivo, B. K. Tan, B. H. Bay, Int. J. Oncol., 2003, 23, 1401–1405.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University, Moyzesova 11, 040 01, Košice, Slovakia

    Jaromír Mikeš, Ján Kleban, Veronika Sačková & Peter Fedoročko

  2. Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65, Brno, Czech Republic

    Viktor Horváth, Alena Vaculová, Alois Kozubík & Jiřina Hofmanová

  3. Department of Pharmacology, Faculty of Medicine, P. J. Šafárik University, Tr. SNP 1, 040 66, Košice, Slovakia

    Erika Jamborová

Authors
  1. Jaromír Mikeš
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ján Kleban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Veronika Sačková
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Viktor Horváth
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erika Jamborová
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alena Vaculová
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alois Kozubík
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jiřina Hofmanová
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peter Fedoročko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Fedoročko.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mikeš, J., Kleban, J., Sačková, V. et al. Necrosis predominates in the cell death of human colon adenocarcinoma HT-29 cells treated under variable conditions of photodynamic therapy with hypericin. Photochem Photobiol Sci 6, 758–766 (2007). https://doi.org/10.1039/b700350a

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/b700350a

Search

Navigation