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conferenceseries
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Volume 3
Diagnostic Pathology: Open Access
ISSN: 2476-2024
Laboratory Medicine 2018
June 25-26, 2018
June 25-26, 2018 | Berlin, Germany
13
th
International Conference on
Laboratory Medicine & Pathology
Dual chemotherapy and photodynamic therapy: A synergistic strategy to improve cancer treatment
Ana Lazaro Carrillo
1
, Bruno M Simões
2
, Robert B Clarke
2
and
Angeles Villanueva
1,3
1
Autonomous University of Madrid, Spain
2
Manchester Cancer Research Centre - University of Manchester, UK
3
IMDEA Nanoscience Institute, Spain
N
owadays different strategies are being introduced in order to enhance photodynamic therapy (PDT) effectiveness, such
as combination of PDT with chemotherapy or improvement of photosensitizer (PS) features. A new combined PDT-
chemotherapy treatment comprising two drugs widespread in clinical research - the hydrophobic zinc(II)-phthalocyanine
(ZnPc) as PS and the common chemotherapeutic agent doxorubicin (DOX) - were tested. Cytotoxicity assay showed that
this combination remarkably increases the effectiveness of the treatment by inducing a synergistic cell death effect (lower
than 10%) when compared to DOX or ZnPc monotherapy (cell surviving around 80%). In addition, annexin-V detection
by flow cytometry, analysis of active caspase-3 and cytochrome c by immunofluorescence and time-lapse videomicroscopy
corroborated a fine-tunable effect depending on light dose, leading to apoptotic or necrotic mechanism of cell death. Using
DCFH-DA (dichlorodihydrofluorescein diacetate) probe, we demonstrate that a significant higher reactive oxygen species
generation into cells was the main cause of the synergistic effect of this combined treatment. Further, mammosphere formation
efficiency assay showed a reduced breast cancer stem cell activity in established cell line and primary cells obtained from
patients, even using DOX at much lower concentration than clinical level. Finally, studies in human breast cancer xenografts
indicated a high efficiency also
in vivo
. All these results provide novel and valuable information that contribute to consider
chemophototherapy as a promising tool in current antitumoral treatments, potentially overcoming resistance to cancer
chemotherapy and targeting cancer stem cells.
Biography
Ana Lazaro Carrillo has completed her PhD from Autonomous University of Madrid (Spain) with mention of best thesis in 2017 granted by SEBC (Spanish Society
of Cell Biology). She is a Teaching Assistant in the Department of Biology, a premier research organization. She has participated in more than 30 international
congresses and more than 70 meetings, workshops and courses. She has published 7 papers in journals of high recognition and has been serving as Reviewer of
repute journals. In addition, she has participated in research and dissemination activities related to Multifun project, funded by the European Union and has been a
Research Member of two projects funded by Spanish Ministry for Economy and Competitiveness. Her research interest include: cell biology; photodynamic therapy
and chemotherapy for cancer treatment; internalization, biocompatibility and efficient delivery of nanostructures
in vitro
(cell cultures); cell death mechanisms and
cellular inactivation; activity of cancer stem cells (established cell lines and patient samples).
ana.lazaro@uam.esAna Lazaro Carrillo et al., Diagn Pathol Open 2018, Volume 3
DOI: 10.4172/2476-2024-C1-002
Figure 1:
Effect in cancer stem cells (CSCs) in MCF-7 cell line. Evaluation of mammosphere formation efficiency in control cells or after the different treatments under
(A)
dark condition or
(B)
irradiated with a light dose of 2 J cm-2.
(C)
Morphology of the mammospheres formed after the different treatments in dark and light condition