Photodynamic synergistic effect of pheophorbide a and doxorubicin in combined treatment against tumoral cells

Rubén Ruiz-González, Paula Milán, Roger Bresolí-Obach, Juan Carlos Stockert, Angeles Villanueva, Magdalena Cañete*, Santi Nonell

*Corresponding author for this work

Research output: Indexed journal article Articlepeer-review

39 Citations (Scopus)

Abstract

A combination of therapies to treat cancer malignancies is at the forefront of research with the aim to reduce drug doses (ultimately side effects) and diminish the possibility of resistance emergence given the multitarget strategy. With this goal in mind, in the present study, we report the combination between the chemotherapeutic drug doxorubicin (DOXO) and the photosensitizing agent pheophorbide a (PhA) to inactivate HeLa cells. Photophysical studies revealed that DOXO can quench the excited states of PhA, detracting from its photosensitizing ability. DOXO can itself photosensitize the production of singlet oxygen; however, this is largely suppressed when bound to DNA. Photodynamic treatments of cells incubated with DOXO and PhA led to different outcomes depending on the concentrations and administration protocols, ranging from antagonistic to synergic for the same concentrations. Taken together, the results indicate that an appropriate combination of DOXO with PhA and red light may produce improved cytotoxicity with a smaller dose of the chemotherapeutic drug, as a result of the different subcellular localization, targets and mode of action of the two agents.

Original languageEnglish
Article number18
Number of pages18
JournalCancers
Volume9
Issue number2
DOIs
Publication statusPublished - 17 Feb 2017

Keywords

  • Doxorubicin
  • HeLa cells
  • Pheophorbide a
  • Photodynamic therapy
  • Synergic treatment

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