Phototoxicity in a laryngeal cancer cell line enhanced by a targeting amphiphilic chlorin photosensitizer

• Published in: Photodiagnosis and photodynamic therapy 2017-09, Vol.19, p.355-362
• Main Authors: Moritz, Milene N.O., Rossa, Carlos, de Oliveira, Kleber T., Uliana, Marciana P., Perussi, Janice R.
• Format: Article
• Language: English
• Subjects: Amphiphilic chlorin; Apoptosis; Apoptosis - drug effects; Cell Death - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Humans; p-53; Perylene - analogs & derivatives; Perylene - pharmacology; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; Phototoxicity; Porphyrins - pharmacology; Tumor cells
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2017.07.003

[Display omitted] •It was demonstrated, for the first time, that the use of a new photosensitizer CHL-T strongly enhances the cytotoxic effect of PDT in HEp-2 cells.•The new CHL-T presents increased intracellular accumulation at low concentrations.•CHL-T increased the percentage of apoptotic cells and also p53 expression in comparison with the use of HY and CHL as photosensitizers.•Significant effect of CHL-T associated with red light irradiation on a cancer cell line, indicating the potential of this new amphiphilic chlorin in enhancing the therapeutic effectiveness of Photodynamic Therapy (PDT). Photodynamic therapy (PDT) has been established in several countries as an alternative therapy for the treatment of various malignancies. This therapy involves the incorporation of a photosensitizer (PS) that is activated by visible light and form reactive oxygen species leading to target cell death by apoptosis or necrosis. Previously, our group has demonstrated that CHL-T (semi-synthesized from chlorophyll a and containing a linked solubilizing group TRISMA®) presented a pronounced potential to induce death in HeLa cell line after PDT. In the present study, besides confirm the high cytotoxicity in another cell line, we have further investigated the cell death mechanisms caused by CHL-T as a photosensitizer in laryngeal carcinoma cells. Cells were exposed to different concentrations of three photosensitizers, namely, hypericin (HY), unmodified chlorin (CHL) and a synthesized amphiphilic chlorin derivative (CHL-T). PSs accumulation and localization were accessed by fluorescence assays. Photosensitization was induced at 6Jcm−2 using red LEDs (630±10nm). Viability was assessed by mitochondrial function (MTT); whereas apoptosis/necrosis was evaluated by fluorescence microscopy and flow cytometry. Expression of pro-apoptotic p53 protein was studied by Western blot. All PS showed similar localization profile in the HEp-2 cells. The use of CHL-T increased the percentage of apoptotic cells and also p53 expression in comparison with the use of HY and CHL as photosensitizers. This study shows a significant effect of CHLT associated with red light (630±10nm and 18mWcm−2) irradiation on a cancer cell line, indicating the potential of this amphiphilic chlorin in enhancing the therapeutic effectiveness of Photodynamic Therapy (PDT).