Bis(3,5-diiodo-2,4,6-trihydroxyphenyl)squaraine photodynamic therapy disrupts redox homeostasis and induce mitochondria-mediated apoptosis in human breast cancer cells

Photodynamic therapy (PDT) is a clinically established and highly evolving treatment modality for cancer. PDT utilizes a light responsive drug called photosensitizer that selectively destroys tumor cells upon light irradiation. Squaraines are a class of dyes possessing all favorable characteristics...

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Bibliographic Details
Published in:Scientific reports 2017-02, Vol.7 (1), p.42126-42126, Article 42126
Main Authors: Saneesh Babu, P. S., Manu, Prasad M., Dhanya, T. Jayaram, Tapas, Pradhan, Meera, R. Nair, Surendran, Arun, Aneesh, Kumar A., Vadakkancheril, S. Jisha, Ramaiah, Danaboyina, Nair, S. Asha, Pillai, M. Radhakrishna
Format: Article
Language:English
Subjects:
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Apoptosis
Breast cancer
Cytotoxicity
Homeostasis
Humanities and Social Sciences
Mitochondria
multidisciplinary
Oxidative stress
Photodynamic therapy
Science
Tumor cells
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Summary:Photodynamic therapy (PDT) is a clinically established and highly evolving treatment modality for cancer. PDT utilizes a light responsive drug called photosensitizer that selectively destroys tumor cells upon light irradiation. Squaraines are a class of dyes possessing all favorable characteristics of a photosensitizer and have been considered to be a potent candidate for next generation PDT. In this study we chose an iodo derivative of squaraine called diiodo-squaraine (bis(3, 5-diiodo-2,4,6-trihydroxyphenyl)squaraine) which has been reported for its tumor specificity but least studied for its cellular and molecular functions. Our studies revealed that the iodo derivative of squaraine possess maximum photodynamic activity in human breast cancer cells MDA- MB- 231 and had very little cytotoxicity in normal breast cells MCF-10A. We analyzed its pro and anti-apoptotic events initiated by oxidative stress exploring a proteomic approach and delineated other critical molecular pathways and key proteins involved in regulating the complex network of cellular response upon PDT. Our study showed that, diiodo- squaraines predominantly accumulate in mitochondria and induce mitochondria-mediated apoptosis. Our study also reveals the novel mechanistic role of diiodo-squaraines to induce oxidative stress there by activating both protective and death inducing pathways post PDT.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep42126