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2017 ; 17
(1
): 194
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Methylene blue photodynamic therapy induces selective and massive cell death in
human breast cancer cells
#MMPMID28298203
Dos Santos AF
; Terra LF
; Wailemann RA
; Oliveira TC
; Gomes VM
; Mineiro MF
; Meotti FC
; Bruni-Cardoso A
; Baptista MS
; Labriola L
BMC Cancer
2017[Mar]; 17
(1
): 194
PMID28298203
show ga
BACKGROUND: Breast cancer is the main cause of mortality among women. The disease
presents high recurrence mainly due to incomplete efficacy of primary treatment
in killing all cancer cells. Photodynamic therapy (PDT), an approach that causes
tissue destruction by visible light in the presence of a photosensitizer (Ps) and
oxygen, appears as a promising alternative therapy that could be used adjunct to
chemotherapy and surgery for curing cancer. However, the efficacy of PDT to treat
breast tumours as well as the molecular mechanisms that lead to cell death remain
unclear. METHODS: In this study, we assessed the cell-killing potential of PDT
using methylene blue (MB-PDT) in three breast epithelial cell lines that
represent non-malignant conditions and different molecular subtypes of breast
tumours. Cells were incubated in the absence or presence of MB and irradiated or
not at 640 nm with 4.5 J/cm(2). We used a combination of imaging and biochemistry
approaches to assess the involvement of classical autophagic and apoptotic
pathways in mediating the cell-deletion induced by MB-PDT. The role of these
pathways was investigated using specific inhibitors, activators and gene
silencing. RESULTS: We observed that MB-PDT differentially induces massive cell
death of tumour cells. Non-malignant cells were significantly more resistant to
the therapy compared to malignant cells. Morphological and biochemical analysis
of dying cells pointed to alternative mechanisms rather than classical apoptosis.
MB-PDT-induced autophagy modulated cell viability depending on the cell model
used. However, impairment of one of these pathways did not prevent the fatal
destination of MB-PDT treated cells. Additionally, when using a physiological 3D
culture model that recapitulates relevant features of normal and tumorous breast
tissue morphology, we found that MB-PDT differential action in killing tumour
cells was even higher than what was detected in 2D cultures. CONCLUSIONS:
Finally, our observations underscore the potential of MB-PDT as a highly
efficient strategy which could use as a powerful adjunct therapy to surgery of
breast tumours, and possibly other types of tumours, to safely increase the
eradication rate of microscopic residual disease and thus minimizing the chance
of both local and metastatic recurrence.