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 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.
Rajiv Gandhi Centre for Biotechnology, Cancer Research Program, Thiruvananthapuram, 695014, India.
P S
PS
Saneesh Babu
Rajiv Gandhi Centre for Biotechnology, Cancer Research Program, Thiruvananthapuram, 695014, India.
Prasad M
PM
Manu
CSIR-National Institute for Interdisciplinary Science and Technology, Photosciences and Photonics, Thiruvananthapuram, 695019, India.
T Jayaram
TJ
Dhanya
Rajiv Gandhi Centre for Biotechnology, Cancer Research Program, Thiruvananthapuram, 695014, India.
Pradhan
P
Tapas
Rajiv Gandhi Centre for Biotechnology, Cancer Research Program, Thiruvananthapuram, 695014, India.
R Nair
RN
Meera
Rajiv Gandhi Centre for Biotechnology Cardiovascular &Diabetes Disease Biology, Thiruvananthapuram, 695014, India.
Arun
A
Surendran
Rajiv Gandhi Centre for Biotechnology Cardiovascular &Diabetes Disease Biology, Thiruvananthapuram, 695014, India.
Kumar A
KA
Aneesh
CSIR-National Institute for Interdisciplinary Science and Technology, Photosciences and Photonics, Thiruvananthapuram, 695019, India.
S Jisha
SJ
Vadakkancheril
CSIR-National Institute for Interdisciplinary Science and Technology, Photosciences and Photonics, Thiruvananthapuram, 695019, India.|CSIR-North East Institute of Science and Technology), Jorhat, 785006, India.
Danaboyina
D
Ramaiah
Rajiv Gandhi Centre for Biotechnology, Cancer Research Program, Thiruvananthapuram, 695014, India.
S Asha
SA
Nair
Rajiv Gandhi Centre for Biotechnology, Cancer Research Program, Thiruvananthapuram, 695014, India.
M Radhakrishna
MR
Pillai
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003503:Cyclobutanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D045325:HCT116 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D009928:Organ Specificity; D010084:Oxidation-Reduction; D061105:Peroxiredoxin III / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
D003503:Cyclobutanes; C497249:DDIT3 protein, human; D018840:HSP70 Heat-Shock Proteins; D010636:Phenols; D017319:Photosensitizing Agents; C532973:bis(3,5-diiodo-2,4,6-trihydroxyphenyl)squaraine; D051742:Transcription Factor CHOP; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D002374:Catalase