Mitochondria and DNA Targeting of 5,10,15,20-Tetrakis(7-sulfonatobenzo[b]thiophene) Porphyrin-Induced Photodynamic Therapy via Intrinsic and Extrinsic Apoptotic Cell Death
Journal of Medicinal Chemistry, ISSN: 1520-4804, Vol: 58, Issue: 17, Page: 6864-6874
2015
- 75Citations
- 52Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations75
- Citation Indexes75
- 75
- CrossRef66
- Captures52
- Readers52
- 52
Article Description
Photodynamic therapy (PDT) selectively targets subcellular organelles and promises an excellent therapeutic strategy for cancer treatment. Here, we report the synthesis of a new water-soluble photosensitizer, 5,10,15,20-tetrakis (7-sulfonatobenzo[b]thiophene) porphyrin (SBTP). Rational design of the porphyrinic molecule containing benzo[b]thiophene moiety at the meso-position led to selective accumulation in both mitochondria and nucleus of MCF-7 cells. This multitarget ability of SBTP can cause damage to mitochondria as well as DNA simultaneously. FACS analysis showed rapid cellular uptake of SBTP. High-content cell-based assay was executed to concurrently monitor increase of cytosolic Ca levels, mitochondrial permeability transition (MPT), and caspase-3/7/8 activation in MCF-7 cells under the pathological condition caused by PDT action of SBTP. The study of cell death dynamics showed that PDT action of SBTP caused an increase in the MPT followed by an increase in cytosolic Ca level. The localization of SBTP in the mitochondria activated the intrinsic apoptotic pathway. Additionally, localization of SBTP in the nucleus led to DNA damage in MCF-7 cells. The DNA fragmentation that occurred by PDT action of SBTP was thought to be responsible for extrinsic apoptosis of MCF-7 cells. SBTP demonstrated effective PDT activity of 5 μM IC value to MCF-7 cells by bitargeting mitochondria and DNA.
Bibliographic Details
American Chemical Society (ACS)
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