4b2f9b8998e3e76ff2e69b2771018c96 pmc_28218672.pdf 111f871924a0a0142577dc09aa1c9fe6958e2ccb pmc_28218672.pdf 1d3c629455bac9215052180267aa66fd16035046d3c364c6ded45bbcc42d375c pmc_28218672.pdf Title: Photodynamic Synergistic Effect of Pheophorbide a and Doxorubicin in Combined Treatment against Tumoral Cells Subject: 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. Keywords: photodynamic therapy; doxorubicin; pheophorbide a; synergic treatment; HeLa cells Author: Rubén Ruiz-González, Paula Milán, Roger Bresolí-Obach, Juan Carlos Stockert, Angeles Villanueva, Magdalena Cañete and Santi Nonell Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.17 CreationDate: Mon Feb 20 02:04:21 2017 CET ModDate: Mon Feb 20 02:04:21 2017 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 11090066 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CNVJUZ+URWPalladioL-Ital Type 1 Custom yes yes no 117 0 JMUIGV+URWPalladioL-Bold Type 1 Custom yes yes no 118 0 WKNAGP+URWPalladioL-Roma Type 1 Custom yes yes no 119 0 WTLQHS+VnURWPalladioL Type 1 Custom yes yes no 120 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 126 0 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