Bis(3,5-diiodo-2,4,6-trihydroxyphenyl)squaraine: a novel candidate in photodynamic therapy for skin cancer models in vivo.
Photodynamic therapy (PDT) is based on the light-induced activation of a photosensitizer generating highly reactive oxygen species that induce tissue destruction in malignant tissues. The present study was carried out to assess the photosensitizing potential of bis(3,5-diiodo-2,4,6-trihydroxyphenyl)squaraine in PDT trials in vivo. Male Swiss albino mice were divided into five groups. Skin tumor was induced using 7,12-dimethylbenz(a)anthracene - DMBA in the animals of Groups II, III, IV and V, while animals of Group I served as the control. At the completion of 20 weeks of induction, the tumor bearing mice from Group III, IV and V were given an intraperitoneal injection with the squaraine dye (12.5mg/kg body weight). After 24h, in the Group IV and V animals, the tumor area was exposed to visible light from a 1000W halogen lamp. The mice from groups I to IV were sacrificed two weeks after the PDT treatment and the marker enzymes (myeloperoxidase [MPO], beta-d-glucuronidase, rhodanese, lactate dehydrogenase [LDH], hexokinase, sialic acid and caspase) were assayed in tumor and normal tissues. Animals from Group V were sacrificed after 90 days of PDT treatment and the above parameters were recorded. Reduction in tumor volume and reversal of biochemical markers to near normal levels were observed in the treatment groups. The study assumes importance as it is the first report on PDT-a novel modality, using a squaraine dye for skin cancer therapy in vivo. The uniqueness of the mode of treatment lies in the selective uptake of squaraine dye by the cancer cells and their selective destruction using PDT without affecting the neighbouring normal cells, which is much advantageous over radiation therapy now frequently used. Also in skin cancer models, the progression/cure can be visualized by the naked eye which is another point of advantage, while seeking new modalities for the treatment of cancer.
Gayathri Devi
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Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, Kerala, India.
Cibin
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Ramaiah
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Abraham
Annie
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003503:Cyclobutanes / Q000627:therapeutic use*; D005966:Glucuronidase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000532:radiotherapy; D009195:Peroxidase / Q000378:metabolism; D010636:Phenols / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000532:radiotherapy*; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism
D003503:Cyclobutanes; D010636:Phenols; D017319:Photosensitizing Agents; C532973:bis(3,5-diiodo-2,4,6-trihydroxyphenyl)squaraine; D015127:9,10-Dimethyl-1,2-benzanthracene; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D006593:Hexokinase; D013884:Thiosulfate Sulfurtransferase; D005966:Glucuronidase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D019158:N-Acetylneuraminic Acid