CONICET | Buscador de Institutos y Recursos Humanos

Photodynamic therapy (PDT) is an anticancer treatment based on light-induced destruction of photosensitized malignant cells and tissues. In recent years, 5-aminolaevulinic acid (ALA), a biochemical precursor of the potent photosensitizer protoporphyrin IX, has been successfully used for fluorescent diagnosis and photodynamic treatment of cancer. PDT is an important treatment for bladder cancer due to the easy light access to the tumour via endoscopy. Silybin, a natural flavonoid obtained from Silybum marianum, is currently used as a liver protector. In addition, our group has reported its antitumour properties per se as well as potentiation of the efficacy of several antitumour treatments. In the present work, we have evaluated the cytotoxicity of the combined treatment, ALAPDT and silybin, in two bladder cancer cell lines: the human T24 and the murine MB49. The cells were exposed to luminic doses inducing 50% of cell death (LD50, expressed in J cm)2). After 19 h of ALA-PDT, the cytotoxicity was evaluated by the MTT method. The T24 cell line is more sensitive to ALA-PDT than the MB49 cell line, the LD50 being 0Æ025 J cm)2 for T24 and 0Æ05 J cm)2 for MB49. The combined treatment consists of ALA-PDT treatment with LD50 of cells pretreated with silybin 24 h before. In the MB49 cells, silybin 50 and 30 lmol L)1 per se induced 37% and 24% cytotoxicity, respectively, whereas the combination with ALAPDT increased the cell death by 25% and 13%. Similar results were obtained for the T24 cell line, but this cell line was less sensitive to silybin treatment. As nontoxic silybin doses do not potentiate the PDT effect and the combined treatment is not synergistic but additive, we conclude that the mechanisms of action of each treatment are different. These results suggest that the combination of silybin and ALA-PDT would increase PDT efficacy.