title: Photodynamic Synergistic Effect of Pheophorbide a and Doxorubicin in Combined Treatment against Tumoral Cells.
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.
authors.affiliation: Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain. ruben.ruiz@iqs.url.edu.
authors.forename: Rubén
authors.initials: R
authors.lastname: Ruiz-González
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin 2, 28049 Cantoblanco-Madrid, Spain. paula.milan@estudiante.uam.es.
authors.forename: Paula
authors.initials: P
authors.lastname: Milán
authors.affiliation: Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain. rogerbresolio@iqs.url.edu.
authors.forename: Roger
authors.initials: R
authors.lastname: Bresolí-Obach
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin 2, 28049 Cantoblanco-Madrid, Spain. juancarlos.stockert@gmail.com.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Stockert
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin 2, 28049 Cantoblanco-Madrid, Spain. angeles.villanueva@uam.es.
authors.forename: Angeles
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin 2, 28049 Cantoblanco-Madrid, Spain. magdalena.canete@uam.es.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cañete
authors.affiliation: Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain. santi.nonell@iqs.url.edu.
authors.forename: Santi
authors.initials: S
authors.lastname: Nonell
keywords: HeLa cells; doxorubicin; pheophorbide a; photodynamic therapy; synergic treatment