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  • Title: Photodynamic effects of porphyrin and chlorin photosensitizers in human colon adenocarcinoma cells.
    Author: Banfi S, Caruso E, Caprioli S, Mazzagatti L, Canti G, Ravizza R, Gariboldi M, Monti E.
    Journal: Bioorg Med Chem; 2004 Sep 15; 12(18):4853-60. PubMed ID: 15336264.
    Abstract:
    Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate wavelength of light, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Photofrin, a complex mixture of porphyrin oligomers has recently received FDA approval for the photodynamic treatment of esophageal and endobronchial carcinoma, but its photodynamic and toxicity profiles are far from ideal. In the present study we evaluated a series of porphyrin-based PSs, some of which newly synthesized by our group, with the aim to identify agents with more favorable characteristics. For the most effective compounds in the porphyrin series, chlorin analogs were also synthesized; for comparison, the screening also included Photofrin. Cytotoxicity studies were performed by the MTT assay on a cultured human colon adenocarcinoma cell line (HCT116); the results indicate that the 3,4,5-trimethoxyphenyl, 3OH- and 4OH-phenyl, and the sulfonamidophenyl derivatives are significantly more potent than Photofrin. Flow cytometric studies and fluorescence microscopy indicate that in PDT-treated HCT116 cells death occurs mainly by apoptosis. In summary, novel PSs described in the present study, belonging both to the porphyrin and chlorin series, have proven more effective than Photofrin in killing colon cancer cells in vitro; extending these observation to in vivo models, particularly regarding the deeper reaching chlorin derivatives, might lead to significant advances in the development of tumor PDT.
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