Dos Santos Et Al. (2017) Methylene Blue Photodynamic Therapy Induces Selective And Massive Cell Deat

marteagal

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Please delete if the study has been posted before.

dos Santos et al. (2017) Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells

MB-PDT: Methylene blue photodynamic therapy
Ps: Photosensitizer


A few excerpts from the Discussion section:

In this study we have demonstrated that MB-PDT induced massive cell death in two human breast cancer cell lines displaying different invasive properties. The highest sensitivity to MB-PDT was observed in MDA-MB-231 cells, used as a model of TNBC, a tumour subtype for which there are no targeted treatments. This effect is very relevant because TNBC tumours are the greatest challenge in breast cancer treatment nowadays [7]. With MB-PDT, we obtained almost 100% of cell death in these malignant cells. Our results are significantly better than the ones obtained in other reports using PDT for treating breast cancer cells [10, 41–43]. Other Ps used in previous studies, such as Mitoxantrone, present dark toxicity, which is not desired for PDT practice [12, 16]. In our study using MB we observed no dark toxicity, a feature which can increase local specificity and safety of the treatment.

In the present work, we have reached a difference of up to 80% of MB-PDT-induced cell death between malignant and normal-like cells.

[W]e hypothesize that apoptosis may not be the predominant process that mediates cell death induced by PDT, but only a by-product of other activated mechanisms [22]. [...] In our study we observed no presence of apoptotic traits under any dose, treatment time, or irradiation intensity used. Additionally, cell viability was not completely restored with the use of caspase inhibitors. Furthermore, MB-PDT action could not be exerted exclusively by apoptosis because MCF-7 cells do not express caspase-3 [52]. Additionally, no increase in caspase-7, -8 or -9 activities was detected in MCF-7 cells upon MB-PDT. In this context, we also observed no decrease in the ratio of anti- and pro-apoptotic proteins and that inhibition of the mitochondrial pore formation increased the sensitivity of the cells to MB-PDT, pointing to a probable mitochondrial-independent cell death pathway. Reinforcing this hypothesis, we showed that MB is not localized or, as already reported, it may be in a reduced state in mitochondria [45], thus strongly suggesting that this organelle is indeed not the primary target for MB-PDT oxidative damage.

Previous studies exploring the subcellular localization of MB indicated that this Ps presents a tendency to accumulate in lysosomes of living cells [45]. We reported here for the first time evidence of differential patterns of lysosomes and MB colocalization in different epithelial cell lines of the same tissue. In view of the organelle-specific initiation of cell death, this data may contribute to explain the differential cellular sensitivity to MB-PDT observed among the three analysed cell lines.

The fact that cancer cells can die through different mechanisms is a relevant clue in the choice and design of anticancer therapies based on molecular targets [55]. We have found that, depending on the cell type, multiple cell death pathways might be activated upon MB-PDT. Indeed, we showed that apoptosis and autophagy are related, but not the main cell death inducing pathways. Moreover, preliminary results from our group are pointing some of the regulated necrosis pathways (i.e. necroptosis) as more relevant mechanisms involved in MB-PDT-induced cell death (data not shown). Since one important aspect for an alternative therapy for cancer treatment is to broaden the spectrum of cell death mechanisms to bypass the different resistance mechanisms displayed by malignant cells, we are at the present time focusing our resources to further dissect the alternative molecular pathways leading to MB-PDT photocytotoxicity.

In sum, MB-PDT holds promise as a useful adjunct to surgery to eliminate microscopic residual malignant cells in the post-surgical tumour bed and prevent local as well as metastatic recurrence without affecting normal tissues. In particular for breast cancer, PDT is not currently being tested as a peri-opertive therapy like the one described for pancreatic cancer (14-15); however, all results presented in this work pointed us the importance to pursue further studies in this direction in a near future. The strategy could be of particular importance in TNBC because meta-static recurrence after surgical tumour resection is a major and frequent cause of patient mortality.
 

Drareg

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Feb 18, 2016
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Very interesting study.
Would be good to know if it was a specific frequency which it appears to be the way it's all going.
 

schultz

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There are a lot of interesting papers on PDT + MB regarding oral bacteria in dental caries. Seems like a safer alternative to chlorhexidine. It is claimed there is no risk of bacterial resistance to it either.

I now "brush" my teeth with a laser... :eek:
 

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