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Kimani, Stanley; Phillips, James; Bruce, James; MacRobert, A. J and Golding, Jon
(2008).
URL: http:\\www.bio.unipd.it/PDT2008
Abstract
Photodynamic therapy (PDT) is based on the preferential uptake and retention of a photosensitizer (PS) in metabolically more active cells then focal light activation of the PS in the presence of molecular oxygen which leads to cytotoxicity. Compared to other cancer therapies, PDT has some advantages in that it spares the tissue architecture, is minimally invasive, does not damage tissue outside the treated area and can be used repeatedly with no serious side effects or development of resistance. However, PDT with the currently approved photosensitizers is not without adverse effects such as prolonged widespread photosensitivity. We propose using glucosamine, a natural glucose analogue widely used as a dietary supplement, to potentiate the PDT effect. Glucosamine was first reported as an inhibitor of tumour growth by Quastel and Cantero in 1953 and various in vivo and in vitro studies have confirmed the inhibitory effect. In our experiments, we used glucosamine together with disulfonated aluminium phthalocyanine (AIPcS2), one of the most clinically effective second-generation photosensitizers, on MCF-7 cell cultures. Dark toxicity and phototoxicity were studied by propidium iodide exclusion assay using fluorescence microscopy and flow cytometry. Dark toxicity was minimal and phototoxicity showed that AIPcS2 in the presence of human physiologically tolerable glucosamine increased cell death by around 15% compared to AIPcS2 alone. Our findings raise the possibility of using a combination of photosensitizers and glucosamine clinically in a simple and cheap way to improve the efficiency of PDT treatment. The combination might therefore help in lowering the dose of photosensitizer that patients need to receive in order to achieve an optimal PDT effect. This has a very important implication in that it can reduce treatment toxicity and other side effects associated with PDT treatment. Further studies are required in order to see if these observations on MCF-7 cell line can be replicated in other established cancer cell lines and in vivo.